id sid tid token lemma pos cord-311035-s3tkbh9r 1 1 key key JJ cord-311035-s3tkbh9r 2 1 : : : cord-311035-s3tkbh9r 2 2 cord-311035-s3tkbh9r cord-311035-s3tkbh9r NNP cord-311035-s3tkbh9r 2 3 authors author NNS cord-311035-s3tkbh9r 2 4 : : : cord-311035-s3tkbh9r 2 5 Procko Procko NNP cord-311035-s3tkbh9r 2 6 , , , cord-311035-s3tkbh9r 2 7 Erik Erik NNP cord-311035-s3tkbh9r 2 8 title title NN cord-311035-s3tkbh9r 2 9 : : : cord-311035-s3tkbh9r 3 1 Deep deep JJ cord-311035-s3tkbh9r 3 2 mutagenesis mutagenesis NN cord-311035-s3tkbh9r 3 3 in in IN cord-311035-s3tkbh9r 3 4 the the DT cord-311035-s3tkbh9r 3 5 study study NN cord-311035-s3tkbh9r 3 6 of of IN cord-311035-s3tkbh9r 3 7 COVID-19 COVID-19 NNP cord-311035-s3tkbh9r 3 8 : : : cord-311035-s3tkbh9r 3 9 a a DT cord-311035-s3tkbh9r 3 10 technical technical JJ cord-311035-s3tkbh9r 3 11 overview overview NN cord-311035-s3tkbh9r 3 12 for for IN cord-311035-s3tkbh9r 3 13 the the DT cord-311035-s3tkbh9r 3 14 proteomics proteomic NNS cord-311035-s3tkbh9r 3 15 community community NN cord-311035-s3tkbh9r 3 16 date date NN cord-311035-s3tkbh9r 3 17 : : : cord-311035-s3tkbh9r 3 18 2020 2020 CD cord-311035-s3tkbh9r 3 19 - - SYM cord-311035-s3tkbh9r 3 20 10 10 CD cord-311035-s3tkbh9r 3 21 - - SYM cord-311035-s3tkbh9r 3 22 21 21 CD cord-311035-s3tkbh9r 3 23 journal journal NN cord-311035-s3tkbh9r 3 24 : : : cord-311035-s3tkbh9r 4 1 Expert expert NN cord-311035-s3tkbh9r 4 2 review review NN cord-311035-s3tkbh9r 4 3 of of IN cord-311035-s3tkbh9r 4 4 proteomics proteomic NNS cord-311035-s3tkbh9r 4 5 DOI doi NN cord-311035-s3tkbh9r 4 6 : : : cord-311035-s3tkbh9r 4 7 10.1080/14789450.2020.1833721 10.1080/14789450.2020.1833721 NNP cord-311035-s3tkbh9r 4 8 sha sha NNP cord-311035-s3tkbh9r 4 9 : : : cord-311035-s3tkbh9r 4 10 1255be96610b4b0bbf06bf283e93e5371df0f474 1255be96610b4b0bbf06bf283e93e5371df0f474 NNP cord-311035-s3tkbh9r 4 11 doc_id doc_id CD cord-311035-s3tkbh9r 4 12 : : : cord-311035-s3tkbh9r 5 1 311035 311035 CD cord-311035-s3tkbh9r 5 2 cord_uid cord_uid NNS cord-311035-s3tkbh9r 5 3 : : : cord-311035-s3tkbh9r 6 1 s3tkbh9r s3tkbh9r : cord-311035-s3tkbh9r 6 2 Introduction introduction NN cord-311035-s3tkbh9r 7 1 The the DT cord-311035-s3tkbh9r 7 2 spike spike NN cord-311035-s3tkbh9r 7 3 ( ( -LRB- cord-311035-s3tkbh9r 7 4 S s NN cord-311035-s3tkbh9r 7 5 ) ) -RRB- cord-311035-s3tkbh9r 7 6 of of IN cord-311035-s3tkbh9r 7 7 SARS SARS NNP cord-311035-s3tkbh9r 7 8 coronavirus coronavirus NN cord-311035-s3tkbh9r 7 9 2 2 CD cord-311035-s3tkbh9r 7 10 ( ( -LRB- cord-311035-s3tkbh9r 7 11 SARS SARS NNP cord-311035-s3tkbh9r 7 12 - - HYPH cord-311035-s3tkbh9r 7 13 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 7 14 ) ) -RRB- cord-311035-s3tkbh9r 7 15 engages engage VBZ cord-311035-s3tkbh9r 7 16 angiotensin angiotensin NN cord-311035-s3tkbh9r 7 17 - - HYPH cord-311035-s3tkbh9r 7 18 converting convert VBG cord-311035-s3tkbh9r 7 19 enzyme enzyme NN cord-311035-s3tkbh9r 7 20 2 2 CD cord-311035-s3tkbh9r 7 21 ( ( -LRB- cord-311035-s3tkbh9r 7 22 ACE2 ACE2 NNP cord-311035-s3tkbh9r 7 23 ) ) -RRB- cord-311035-s3tkbh9r 7 24 on on IN cord-311035-s3tkbh9r 7 25 a a DT cord-311035-s3tkbh9r 7 26 host host NN cord-311035-s3tkbh9r 7 27 cell cell NN cord-311035-s3tkbh9r 7 28 to to TO cord-311035-s3tkbh9r 7 29 trigger trigger VB cord-311035-s3tkbh9r 7 30 viral viral JJ cord-311035-s3tkbh9r 7 31 - - HYPH cord-311035-s3tkbh9r 7 32 cell cell NN cord-311035-s3tkbh9r 7 33 membrane membrane NN cord-311035-s3tkbh9r 7 34 fusion fusion NN cord-311035-s3tkbh9r 7 35 and and CC cord-311035-s3tkbh9r 7 36 infection infection NN cord-311035-s3tkbh9r 7 37 . . . cord-311035-s3tkbh9r 8 1 The the DT cord-311035-s3tkbh9r 8 2 extracellular extracellular JJ cord-311035-s3tkbh9r 8 3 region region NN cord-311035-s3tkbh9r 8 4 of of IN cord-311035-s3tkbh9r 8 5 ACE2 ACE2 NNP cord-311035-s3tkbh9r 8 6 can can MD cord-311035-s3tkbh9r 8 7 be be VB cord-311035-s3tkbh9r 8 8 administered administer VBN cord-311035-s3tkbh9r 8 9 as as IN cord-311035-s3tkbh9r 8 10 a a DT cord-311035-s3tkbh9r 8 11 soluble soluble JJ cord-311035-s3tkbh9r 8 12 decoy decoy NN cord-311035-s3tkbh9r 8 13 to to TO cord-311035-s3tkbh9r 8 14 compete compete VB cord-311035-s3tkbh9r 8 15 for for IN cord-311035-s3tkbh9r 8 16 binding bind VBG cord-311035-s3tkbh9r 8 17 sites site NNS cord-311035-s3tkbh9r 8 18 on on IN cord-311035-s3tkbh9r 8 19 the the DT cord-311035-s3tkbh9r 8 20 receptor receptor NN cord-311035-s3tkbh9r 8 21 - - HYPH cord-311035-s3tkbh9r 8 22 binding bind VBG cord-311035-s3tkbh9r 8 23 domain domain NN cord-311035-s3tkbh9r 8 24 ( ( -LRB- cord-311035-s3tkbh9r 8 25 RBD RBD NNP cord-311035-s3tkbh9r 8 26 ) ) -RRB- cord-311035-s3tkbh9r 8 27 of of IN cord-311035-s3tkbh9r 8 28 S S NNP cord-311035-s3tkbh9r 8 29 , , , cord-311035-s3tkbh9r 8 30 but but CC cord-311035-s3tkbh9r 8 31 it -PRON- PRP cord-311035-s3tkbh9r 8 32 has have VBZ cord-311035-s3tkbh9r 8 33 only only RB cord-311035-s3tkbh9r 8 34 moderate moderate JJ cord-311035-s3tkbh9r 8 35 affinity affinity NN cord-311035-s3tkbh9r 8 36 and and CC cord-311035-s3tkbh9r 8 37 efficacy efficacy NN cord-311035-s3tkbh9r 8 38 . . . cord-311035-s3tkbh9r 9 1 The the DT cord-311035-s3tkbh9r 9 2 RBD RBD NNP cord-311035-s3tkbh9r 9 3 , , , cord-311035-s3tkbh9r 9 4 which which WDT cord-311035-s3tkbh9r 9 5 is be VBZ cord-311035-s3tkbh9r 9 6 targeted target VBN cord-311035-s3tkbh9r 9 7 by by IN cord-311035-s3tkbh9r 9 8 neutralizing neutralize VBG cord-311035-s3tkbh9r 9 9 antibodies antibody NNS cord-311035-s3tkbh9r 9 10 , , , cord-311035-s3tkbh9r 9 11 may may MD cord-311035-s3tkbh9r 9 12 also also RB cord-311035-s3tkbh9r 9 13 change change VB cord-311035-s3tkbh9r 9 14 and and CC cord-311035-s3tkbh9r 9 15 adapt adapt VB cord-311035-s3tkbh9r 9 16 through through IN cord-311035-s3tkbh9r 9 17 mutation mutation NN cord-311035-s3tkbh9r 9 18 as as IN cord-311035-s3tkbh9r 9 19 SARS SARS NNP cord-311035-s3tkbh9r 9 20 - - HYPH cord-311035-s3tkbh9r 9 21 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 9 22 becomes become VBZ cord-311035-s3tkbh9r 9 23 endemic endemic JJ cord-311035-s3tkbh9r 9 24 , , , cord-311035-s3tkbh9r 9 25 posing pose VBG cord-311035-s3tkbh9r 9 26 challenges challenge NNS cord-311035-s3tkbh9r 9 27 for for IN cord-311035-s3tkbh9r 9 28 therapeutic therapeutic JJ cord-311035-s3tkbh9r 9 29 and and CC cord-311035-s3tkbh9r 9 30 vaccine vaccine NN cord-311035-s3tkbh9r 9 31 development development NN cord-311035-s3tkbh9r 9 32 . . . cord-311035-s3tkbh9r 10 1 Areas area NNS cord-311035-s3tkbh9r 10 2 Covered cover VBN cord-311035-s3tkbh9r 10 3 Deep deep JJ cord-311035-s3tkbh9r 10 4 mutagenesis mutagenesis NN cord-311035-s3tkbh9r 10 5 is be VBZ cord-311035-s3tkbh9r 10 6 a a DT cord-311035-s3tkbh9r 10 7 Big Big NNP cord-311035-s3tkbh9r 10 8 Data data NN cord-311035-s3tkbh9r 10 9 approach approach NN cord-311035-s3tkbh9r 10 10 to to IN cord-311035-s3tkbh9r 10 11 characterizing characterize VBG cord-311035-s3tkbh9r 10 12 sequence sequence NN cord-311035-s3tkbh9r 10 13 variants variant NNS cord-311035-s3tkbh9r 10 14 . . . cord-311035-s3tkbh9r 11 1 A a DT cord-311035-s3tkbh9r 11 2 deep deep JJ cord-311035-s3tkbh9r 11 3 mutational mutational JJ cord-311035-s3tkbh9r 11 4 scan scan NN cord-311035-s3tkbh9r 11 5 of of IN cord-311035-s3tkbh9r 11 6 ACE2 ACE2 NNP cord-311035-s3tkbh9r 11 7 expressed express VBD cord-311035-s3tkbh9r 11 8 on on IN cord-311035-s3tkbh9r 11 9 human human JJ cord-311035-s3tkbh9r 11 10 cells cell NNS cord-311035-s3tkbh9r 11 11 identified identify VBN cord-311035-s3tkbh9r 11 12 mutations mutation NNS cord-311035-s3tkbh9r 11 13 that that WDT cord-311035-s3tkbh9r 11 14 increase increase VBP cord-311035-s3tkbh9r 11 15 S s NN cord-311035-s3tkbh9r 11 16 affinity affinity NN cord-311035-s3tkbh9r 11 17 and and CC cord-311035-s3tkbh9r 11 18 guided guide VBD cord-311035-s3tkbh9r 11 19 the the DT cord-311035-s3tkbh9r 11 20 engineering engineering NN cord-311035-s3tkbh9r 11 21 of of IN cord-311035-s3tkbh9r 11 22 a a DT cord-311035-s3tkbh9r 11 23 potent potent JJ cord-311035-s3tkbh9r 11 24 and and CC cord-311035-s3tkbh9r 11 25 broad broad JJ cord-311035-s3tkbh9r 11 26 soluble soluble JJ cord-311035-s3tkbh9r 11 27 receptor receptor NN cord-311035-s3tkbh9r 11 28 decoy decoy NN cord-311035-s3tkbh9r 11 29 . . . cord-311035-s3tkbh9r 12 1 A a DT cord-311035-s3tkbh9r 12 2 deep deep JJ cord-311035-s3tkbh9r 12 3 mutational mutational JJ cord-311035-s3tkbh9r 12 4 scan scan NN cord-311035-s3tkbh9r 12 5 of of IN cord-311035-s3tkbh9r 12 6 the the DT cord-311035-s3tkbh9r 12 7 RBD RBD NNP cord-311035-s3tkbh9r 12 8 displayed display VBD cord-311035-s3tkbh9r 12 9 on on IN cord-311035-s3tkbh9r 12 10 the the DT cord-311035-s3tkbh9r 12 11 surface surface NN cord-311035-s3tkbh9r 12 12 of of IN cord-311035-s3tkbh9r 12 13 yeast yeast NN cord-311035-s3tkbh9r 12 14 has have VBZ cord-311035-s3tkbh9r 12 15 revealed reveal VBN cord-311035-s3tkbh9r 12 16 residues residue NNS cord-311035-s3tkbh9r 12 17 tolerant tolerant JJ cord-311035-s3tkbh9r 12 18 of of IN cord-311035-s3tkbh9r 12 19 mutational mutational JJ cord-311035-s3tkbh9r 12 20 changes change NNS cord-311035-s3tkbh9r 12 21 that that WDT cord-311035-s3tkbh9r 12 22 may may MD cord-311035-s3tkbh9r 12 23 act act VB cord-311035-s3tkbh9r 12 24 as as IN cord-311035-s3tkbh9r 12 25 a a DT cord-311035-s3tkbh9r 12 26 source source NN cord-311035-s3tkbh9r 12 27 for for IN cord-311035-s3tkbh9r 12 28 drug drug NN cord-311035-s3tkbh9r 12 29 resistance resistance NN cord-311035-s3tkbh9r 12 30 and and CC cord-311035-s3tkbh9r 12 31 antigenic antigenic JJ cord-311035-s3tkbh9r 12 32 drift drift NN cord-311035-s3tkbh9r 12 33 . . . cord-311035-s3tkbh9r 13 1 Expert Expert NNP cord-311035-s3tkbh9r 13 2 Opinion Opinion NNP cord-311035-s3tkbh9r 13 3 Deep Deep NNP cord-311035-s3tkbh9r 13 4 mutagenesis mutagenesis NN cord-311035-s3tkbh9r 13 5 requires require VBZ cord-311035-s3tkbh9r 13 6 a a DT cord-311035-s3tkbh9r 13 7 selection selection NN cord-311035-s3tkbh9r 13 8 of of IN cord-311035-s3tkbh9r 13 9 diverse diverse JJ cord-311035-s3tkbh9r 13 10 sequence sequence NN cord-311035-s3tkbh9r 13 11 variants variant NNS cord-311035-s3tkbh9r 13 12 ; ; : cord-311035-s3tkbh9r 13 13 an an DT cord-311035-s3tkbh9r 13 14 in in FW cord-311035-s3tkbh9r 13 15 vitro vitro FW cord-311035-s3tkbh9r 13 16 evolution evolution NN cord-311035-s3tkbh9r 13 17 experiment experiment NN cord-311035-s3tkbh9r 13 18 that that WDT cord-311035-s3tkbh9r 13 19 is be VBZ cord-311035-s3tkbh9r 13 20 tracked track VBN cord-311035-s3tkbh9r 13 21 with with IN cord-311035-s3tkbh9r 13 22 next next JJ cord-311035-s3tkbh9r 13 23 - - HYPH cord-311035-s3tkbh9r 13 24 generation generation NN cord-311035-s3tkbh9r 13 25 sequencing sequencing NN cord-311035-s3tkbh9r 13 26 . . . cord-311035-s3tkbh9r 14 1 The the DT cord-311035-s3tkbh9r 14 2 choice choice NN cord-311035-s3tkbh9r 14 3 of of IN cord-311035-s3tkbh9r 14 4 expression expression NN cord-311035-s3tkbh9r 14 5 system system NN cord-311035-s3tkbh9r 14 6 , , , cord-311035-s3tkbh9r 14 7 diversity diversity NN cord-311035-s3tkbh9r 14 8 of of IN cord-311035-s3tkbh9r 14 9 the the DT cord-311035-s3tkbh9r 14 10 variant variant JJ cord-311035-s3tkbh9r 14 11 library library NN cord-311035-s3tkbh9r 14 12 and and CC cord-311035-s3tkbh9r 14 13 selection selection NN cord-311035-s3tkbh9r 14 14 strategy strategy NN cord-311035-s3tkbh9r 14 15 have have VBP cord-311035-s3tkbh9r 14 16 important important JJ cord-311035-s3tkbh9r 14 17 consequences consequence NNS cord-311035-s3tkbh9r 14 18 for for IN cord-311035-s3tkbh9r 14 19 data data NN cord-311035-s3tkbh9r 14 20 quality quality NN cord-311035-s3tkbh9r 14 21 and and CC cord-311035-s3tkbh9r 14 22 interpretation interpretation NN cord-311035-s3tkbh9r 14 23 . . . cord-311035-s3tkbh9r 15 1 Investigations investigation NNS cord-311035-s3tkbh9r 15 2 of of IN cord-311035-s3tkbh9r 15 3 protein protein NN cord-311035-s3tkbh9r 15 4 mutations mutation NNS cord-311035-s3tkbh9r 15 5 have have VBP cord-311035-s3tkbh9r 15 6 classically classically RB cord-311035-s3tkbh9r 15 7 been be VBN cord-311035-s3tkbh9r 15 8 approached approach VBN cord-311035-s3tkbh9r 15 9 by by IN cord-311035-s3tkbh9r 15 10 precision precision NN cord-311035-s3tkbh9r 15 11 targeting targeting NN cord-311035-s3tkbh9r 15 12 , , , cord-311035-s3tkbh9r 15 13 in in IN cord-311035-s3tkbh9r 15 14 which which WDT cord-311035-s3tkbh9r 15 15 a a DT cord-311035-s3tkbh9r 15 16 small small JJ cord-311035-s3tkbh9r 15 17 number number NN cord-311035-s3tkbh9r 15 18 of of IN cord-311035-s3tkbh9r 15 19 mutations mutation NNS cord-311035-s3tkbh9r 15 20 are be VBP cord-311035-s3tkbh9r 15 21 deliberately deliberately RB cord-311035-s3tkbh9r 15 22 introduced introduce VBN cord-311035-s3tkbh9r 15 23 and and CC cord-311035-s3tkbh9r 15 24 tested test VBN cord-311035-s3tkbh9r 15 25 individually individually RB cord-311035-s3tkbh9r 15 26 . . . cord-311035-s3tkbh9r 16 1 This this DT cord-311035-s3tkbh9r 16 2 requires require VBZ cord-311035-s3tkbh9r 16 3 preconceived preconceived JJ cord-311035-s3tkbh9r 16 4 ideas idea NNS cord-311035-s3tkbh9r 16 5 or or CC cord-311035-s3tkbh9r 16 6 hypotheses hypothesis NNS cord-311035-s3tkbh9r 16 7 on on IN cord-311035-s3tkbh9r 16 8 which which WDT cord-311035-s3tkbh9r 16 9 residues residue NNS cord-311035-s3tkbh9r 16 10 and and CC cord-311035-s3tkbh9r 16 11 what what WP cord-311035-s3tkbh9r 16 12 changes change VBZ cord-311035-s3tkbh9r 16 13 to to IN cord-311035-s3tkbh9r 16 14 those those DT cord-311035-s3tkbh9r 16 15 residues residue NNS cord-311035-s3tkbh9r 16 16 might may MD cord-311035-s3tkbh9r 16 17 be be VB cord-311035-s3tkbh9r 16 18 relevant relevant JJ cord-311035-s3tkbh9r 16 19 . . . cord-311035-s3tkbh9r 17 1 When when WRB cord-311035-s3tkbh9r 17 2 the the DT cord-311035-s3tkbh9r 17 3 important important JJ cord-311035-s3tkbh9r 17 4 residues residue NNS cord-311035-s3tkbh9r 17 5 in in IN cord-311035-s3tkbh9r 17 6 a a DT cord-311035-s3tkbh9r 17 7 protein protein NN cord-311035-s3tkbh9r 17 8 sequence sequence NN cord-311035-s3tkbh9r 17 9 are be VBP cord-311035-s3tkbh9r 17 10 unknown unknown JJ cord-311035-s3tkbh9r 17 11 , , , cord-311035-s3tkbh9r 17 12 screens screen NNS cord-311035-s3tkbh9r 17 13 and and CC cord-311035-s3tkbh9r 17 14 selections selection NNS cord-311035-s3tkbh9r 17 15 can can MD cord-311035-s3tkbh9r 17 16 be be VB cord-311035-s3tkbh9r 17 17 used use VBN cord-311035-s3tkbh9r 17 18 instead instead RB cord-311035-s3tkbh9r 17 19 , , , cord-311035-s3tkbh9r 17 20 in in IN cord-311035-s3tkbh9r 17 21 which which WDT cord-311035-s3tkbh9r 17 22 a a DT cord-311035-s3tkbh9r 17 23 library library NN cord-311035-s3tkbh9r 17 24 of of IN cord-311035-s3tkbh9r 17 25 random random JJ cord-311035-s3tkbh9r 17 26 mutations mutation NNS cord-311035-s3tkbh9r 17 27 is be VBZ cord-311035-s3tkbh9r 17 28 in in IN cord-311035-s3tkbh9r 17 29 some some DT cord-311035-s3tkbh9r 17 30 way way NN cord-311035-s3tkbh9r 17 31 sorted sort VBN cord-311035-s3tkbh9r 17 32 to to TO cord-311035-s3tkbh9r 17 33 enrich enrich VB cord-311035-s3tkbh9r 17 34 for for IN cord-311035-s3tkbh9r 17 35 a a DT cord-311035-s3tkbh9r 17 36 small small JJ cord-311035-s3tkbh9r 17 37 number number NN cord-311035-s3tkbh9r 17 38 of of IN cord-311035-s3tkbh9r 17 39 mutants mutant NNS cord-311035-s3tkbh9r 17 40 with with IN cord-311035-s3tkbh9r 17 41 the the DT cord-311035-s3tkbh9r 17 42 intended intended JJ cord-311035-s3tkbh9r 17 43 phenotype phenotype NN cord-311035-s3tkbh9r 17 44 . . . cord-311035-s3tkbh9r 18 1 Both both DT cord-311035-s3tkbh9r 18 2 experiments experiment NNS cord-311035-s3tkbh9r 18 3 are be VBP cord-311035-s3tkbh9r 18 4 limited limit VBN cord-311035-s3tkbh9r 18 5 in in IN cord-311035-s3tkbh9r 18 6 the the DT cord-311035-s3tkbh9r 18 7 scale scale NN cord-311035-s3tkbh9r 18 8 of of IN cord-311035-s3tkbh9r 18 9 information information NN cord-311035-s3tkbh9r 18 10 they -PRON- PRP cord-311035-s3tkbh9r 18 11 provide provide VBP cord-311035-s3tkbh9r 18 12 . . . cord-311035-s3tkbh9r 19 1 Deep deep JJ cord-311035-s3tkbh9r 19 2 mutagenesis mutagenesis NN cord-311035-s3tkbh9r 19 3 or or CC cord-311035-s3tkbh9r 19 4 deep deep JJ cord-311035-s3tkbh9r 19 5 mutational mutational JJ cord-311035-s3tkbh9r 19 6 scanning scanning NN cord-311035-s3tkbh9r 19 7 take take VBP cord-311035-s3tkbh9r 19 8 advantage advantage NN cord-311035-s3tkbh9r 19 9 of of IN cord-311035-s3tkbh9r 19 10 next next JJ cord-311035-s3tkbh9r 19 11 - - HYPH cord-311035-s3tkbh9r 19 12 generation generation NN cord-311035-s3tkbh9r 19 13 sequencing sequencing NN cord-311035-s3tkbh9r 19 14 to to TO cord-311035-s3tkbh9r 19 15 bring bring VB cord-311035-s3tkbh9r 19 16 experimental experimental JJ cord-311035-s3tkbh9r 19 17 protein protein NN cord-311035-s3tkbh9r 19 18 mutagenesis mutagenesis NN cord-311035-s3tkbh9r 19 19 to to IN cord-311035-s3tkbh9r 19 20 the the DT cord-311035-s3tkbh9r 19 21 realm realm NN cord-311035-s3tkbh9r 19 22 of of IN cord-311035-s3tkbh9r 19 23 Big Big NNP cord-311035-s3tkbh9r 19 24 Data Data NNP cord-311035-s3tkbh9r 19 25 [ [ -LRB- cord-311035-s3tkbh9r 19 26 1 1 CD cord-311035-s3tkbh9r 19 27 ] ] -RRB- cord-311035-s3tkbh9r 19 28 . . . cord-311035-s3tkbh9r 20 1 A a DT cord-311035-s3tkbh9r 20 2 screen screen NN cord-311035-s3tkbh9r 20 3 or or CC cord-311035-s3tkbh9r 20 4 selection selection NN cord-311035-s3tkbh9r 20 5 of of IN cord-311035-s3tkbh9r 20 6 a a DT cord-311035-s3tkbh9r 20 7 diverse diverse JJ cord-311035-s3tkbh9r 20 8 library library NN cord-311035-s3tkbh9r 20 9 of of IN cord-311035-s3tkbh9r 20 10 variants variant NNS cord-311035-s3tkbh9r 20 11 is be VBZ cord-311035-s3tkbh9r 20 12 tracked track VBN cord-311035-s3tkbh9r 20 13 by by IN cord-311035-s3tkbh9r 20 14 next next JJ cord-311035-s3tkbh9r 20 15 - - HYPH cord-311035-s3tkbh9r 20 16 generation generation NN cord-311035-s3tkbh9r 20 17 sequencing sequencing NN cord-311035-s3tkbh9r 20 18 to to TO cord-311035-s3tkbh9r 20 19 observe observe VB cord-311035-s3tkbh9r 20 20 how how WRB cord-311035-s3tkbh9r 20 21 the the DT cord-311035-s3tkbh9r 20 22 population population NN cord-311035-s3tkbh9r 20 23 's 's POS cord-311035-s3tkbh9r 20 24 genetic genetic JJ cord-311035-s3tkbh9r 20 25 makeup makeup NN cord-311035-s3tkbh9r 20 26 changes change NNS cord-311035-s3tkbh9r 20 27 . . . cord-311035-s3tkbh9r 21 1 Mutations mutation NNS cord-311035-s3tkbh9r 21 2 with with IN cord-311035-s3tkbh9r 21 3 enhanced enhanced JJ cord-311035-s3tkbh9r 21 4 function function NN cord-311035-s3tkbh9r 21 5 are be VBP cord-311035-s3tkbh9r 21 6 enriched enrich VBN cord-311035-s3tkbh9r 21 7 , , , cord-311035-s3tkbh9r 21 8 while while IN cord-311035-s3tkbh9r 21 9 deleterious deleterious JJ cord-311035-s3tkbh9r 21 10 mutations mutation NNS cord-311035-s3tkbh9r 21 11 are be VBP cord-311035-s3tkbh9r 21 12 depleted deplete VBN cord-311035-s3tkbh9r 21 13 ; ; : cord-311035-s3tkbh9r 21 14 the the DT cord-311035-s3tkbh9r 21 15 enrichment enrichment NN cord-311035-s3tkbh9r 21 16 ratio ratio NN cord-311035-s3tkbh9r 21 17 comparing compare VBG cord-311035-s3tkbh9r 21 18 frequencies frequency NNS cord-311035-s3tkbh9r 21 19 in in IN cord-311035-s3tkbh9r 21 20 the the DT cord-311035-s3tkbh9r 21 21 selected select VBN cord-311035-s3tkbh9r 21 22 population population NN cord-311035-s3tkbh9r 21 23 with with IN cord-311035-s3tkbh9r 21 24 the the DT cord-311035-s3tkbh9r 21 25 naive naive JJ cord-311035-s3tkbh9r 21 26 library library NN cord-311035-s3tkbh9r 21 27 thus thus RB cord-311035-s3tkbh9r 21 28 acts act VBZ cord-311035-s3tkbh9r 21 29 as as IN cord-311035-s3tkbh9r 21 30 a a DT cord-311035-s3tkbh9r 21 31 proxy proxy NN cord-311035-s3tkbh9r 21 32 for for IN cord-311035-s3tkbh9r 21 33 relative relative JJ cord-311035-s3tkbh9r 21 34 phenotype phenotype NN cord-311035-s3tkbh9r 21 35 . . . cord-311035-s3tkbh9r 22 1 Now now RB cord-311035-s3tkbh9r 22 2 , , , cord-311035-s3tkbh9r 22 3 the the DT cord-311035-s3tkbh9r 22 4 relative relative JJ cord-311035-s3tkbh9r 22 5 effects effect NNS cord-311035-s3tkbh9r 22 6 of of IN cord-311035-s3tkbh9r 22 7 thousands thousand NNS cord-311035-s3tkbh9r 22 8 of of IN cord-311035-s3tkbh9r 22 9 mutations mutation NNS cord-311035-s3tkbh9r 22 10 can can MD cord-311035-s3tkbh9r 22 11 be be VB cord-311035-s3tkbh9r 22 12 assessed assess VBN cord-311035-s3tkbh9r 22 13 simultaneously simultaneously RB cord-311035-s3tkbh9r 22 14 in in IN cord-311035-s3tkbh9r 22 15 a a DT cord-311035-s3tkbh9r 22 16 single single JJ cord-311035-s3tkbh9r 22 17 experiment experiment NN cord-311035-s3tkbh9r 22 18 and and CC cord-311035-s3tkbh9r 22 19 a a DT cord-311035-s3tkbh9r 22 20 comprehensive comprehensive JJ cord-311035-s3tkbh9r 22 21 mutational mutational JJ cord-311035-s3tkbh9r 22 22 landscape landscape NN cord-311035-s3tkbh9r 22 23 can can MD cord-311035-s3tkbh9r 22 24 be be VB cord-311035-s3tkbh9r 22 25 calculated calculate VBN cord-311035-s3tkbh9r 22 26 from from IN cord-311035-s3tkbh9r 22 27 experimental experimental JJ cord-311035-s3tkbh9r 22 28 data datum NNS cord-311035-s3tkbh9r 22 29 . . . cord-311035-s3tkbh9r 23 1 Deep deep JJ cord-311035-s3tkbh9r 23 2 mutagenesis mutagenesis NN cord-311035-s3tkbh9r 23 3 has have VBZ cord-311035-s3tkbh9r 23 4 been be VBN cord-311035-s3tkbh9r 23 5 developed develop VBN cord-311035-s3tkbh9r 23 6 by by IN cord-311035-s3tkbh9r 23 7 multiple multiple JJ cord-311035-s3tkbh9r 23 8 groups group NNS cord-311035-s3tkbh9r 23 9 over over IN cord-311035-s3tkbh9r 23 10 the the DT cord-311035-s3tkbh9r 23 11 past past JJ cord-311035-s3tkbh9r 23 12 decade decade NN cord-311035-s3tkbh9r 23 13 [ [ -LRB- cord-311035-s3tkbh9r 23 14 2 2 CD cord-311035-s3tkbh9r 23 15 ] ] -RRB- cord-311035-s3tkbh9r 23 16 [ [ -LRB- cord-311035-s3tkbh9r 23 17 3 3 CD cord-311035-s3tkbh9r 23 18 ] ] -RRB- cord-311035-s3tkbh9r 23 19 [ [ -LRB- cord-311035-s3tkbh9r 23 20 4 4 CD cord-311035-s3tkbh9r 23 21 ] ] -RRB- cord-311035-s3tkbh9r 23 22 [ [ -LRB- cord-311035-s3tkbh9r 23 23 5 5 CD cord-311035-s3tkbh9r 23 24 ] ] -RRB- cord-311035-s3tkbh9r 23 25 [ [ -LRB- cord-311035-s3tkbh9r 23 26 6 6 CD cord-311035-s3tkbh9r 23 27 ] ] -RRB- cord-311035-s3tkbh9r 23 28 [ [ -LRB- cord-311035-s3tkbh9r 23 29 7 7 CD cord-311035-s3tkbh9r 23 30 ] ] -RRB- cord-311035-s3tkbh9r 24 1 [ [ -LRB- cord-311035-s3tkbh9r 24 2 8 8 CD cord-311035-s3tkbh9r 24 3 ] ] -RRB- cord-311035-s3tkbh9r 24 4 [ [ -LRB- cord-311035-s3tkbh9r 24 5 9 9 CD cord-311035-s3tkbh9r 24 6 ] ] -RRB- cord-311035-s3tkbh9r 24 7 [ [ -LRB- cord-311035-s3tkbh9r 24 8 10 10 CD cord-311035-s3tkbh9r 24 9 ] ] -RRB- cord-311035-s3tkbh9r 24 10 [ [ -LRB- cord-311035-s3tkbh9r 24 11 11 11 CD cord-311035-s3tkbh9r 24 12 ] ] -RRB- cord-311035-s3tkbh9r 25 1 [ [ -LRB- cord-311035-s3tkbh9r 25 2 12 12 CD cord-311035-s3tkbh9r 25 3 ] ] -RRB- cord-311035-s3tkbh9r 25 4 [ [ -LRB- cord-311035-s3tkbh9r 25 5 13 13 CD cord-311035-s3tkbh9r 25 6 ] ] -RRB- cord-311035-s3tkbh9r 25 7 and and CC cord-311035-s3tkbh9r 25 8 has have VBZ cord-311035-s3tkbh9r 25 9 proven prove VBN cord-311035-s3tkbh9r 25 10 especially especially RB cord-311035-s3tkbh9r 25 11 invaluable invaluable JJ cord-311035-s3tkbh9r 25 12 to to TO cord-311035-s3tkbh9r 25 13 meet meet VB cord-311035-s3tkbh9r 25 14 three three CD cord-311035-s3tkbh9r 25 15 goals goal NNS cord-311035-s3tkbh9r 25 16 : : : cord-311035-s3tkbh9r 25 17 assisting assist VBG cord-311035-s3tkbh9r 25 18 protein protein NN cord-311035-s3tkbh9r 25 19 engineering engineering NN cord-311035-s3tkbh9r 25 20 , , , cord-311035-s3tkbh9r 25 21 understanding understand VBG cord-311035-s3tkbh9r 25 22 mutational mutational JJ cord-311035-s3tkbh9r 25 23 tolerance tolerance NN cord-311035-s3tkbh9r 25 24 within within IN cord-311035-s3tkbh9r 25 25 a a DT cord-311035-s3tkbh9r 25 26 protein protein NN cord-311035-s3tkbh9r 25 27 sequence sequence NN cord-311035-s3tkbh9r 25 28 , , , cord-311035-s3tkbh9r 25 29 and and CC cord-311035-s3tkbh9r 25 30 predicting predict VBG cord-311035-s3tkbh9r 25 31 which which WDT cord-311035-s3tkbh9r 25 32 mutations mutation NNS cord-311035-s3tkbh9r 25 33 might may MD cord-311035-s3tkbh9r 25 34 be be VB cord-311035-s3tkbh9r 25 35 associated associate VBN cord-311035-s3tkbh9r 25 36 with with IN cord-311035-s3tkbh9r 25 37 adverse adverse JJ cord-311035-s3tkbh9r 25 38 disease disease NN cord-311035-s3tkbh9r 25 39 outcomes outcome NNS cord-311035-s3tkbh9r 25 40 , , , cord-311035-s3tkbh9r 25 41 especially especially RB cord-311035-s3tkbh9r 25 42 in in IN cord-311035-s3tkbh9r 25 43 the the DT cord-311035-s3tkbh9r 25 44 context context NN cord-311035-s3tkbh9r 25 45 of of IN cord-311035-s3tkbh9r 25 46 cancer cancer NN cord-311035-s3tkbh9r 25 47 or or CC cord-311035-s3tkbh9r 25 48 drug drug NN cord-311035-s3tkbh9r 25 49 resistance resistance NN cord-311035-s3tkbh9r 25 50 . . . cord-311035-s3tkbh9r 26 1 Two two CD cord-311035-s3tkbh9r 26 2 recent recent JJ cord-311035-s3tkbh9r 26 3 and and CC cord-311035-s3tkbh9r 26 4 prominent prominent JJ cord-311035-s3tkbh9r 26 5 studies study NNS cord-311035-s3tkbh9r 26 6 of of IN cord-311035-s3tkbh9r 26 7 SARS SARS NNP cord-311035-s3tkbh9r 26 8 coronavirus coronavirus NN cord-311035-s3tkbh9r 26 9 2 2 CD cord-311035-s3tkbh9r 27 1 ( ( -LRB- cord-311035-s3tkbh9r 27 2 SARS SARS NNP cord-311035-s3tkbh9r 27 3 - - HYPH cord-311035-s3tkbh9r 27 4 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 27 5 ) ) -RRB- cord-311035-s3tkbh9r 27 6 have have VBP cord-311035-s3tkbh9r 27 7 used use VBN cord-311035-s3tkbh9r 27 8 deep deep JJ cord-311035-s3tkbh9r 27 9 mutagenesis mutagenesis NN cord-311035-s3tkbh9r 27 10 to to TO cord-311035-s3tkbh9r 27 11 address address VB cord-311035-s3tkbh9r 27 12 each each DT cord-311035-s3tkbh9r 27 13 of of IN cord-311035-s3tkbh9r 27 14 these these DT cord-311035-s3tkbh9r 27 15 problems problem NNS cord-311035-s3tkbh9r 27 16 [ [ -LRB- cord-311035-s3tkbh9r 27 17 14 14 CD cord-311035-s3tkbh9r 27 18 , , , cord-311035-s3tkbh9r 27 19 15 15 CD cord-311035-s3tkbh9r 27 20 ] ] -RRB- cord-311035-s3tkbh9r 27 21 . . . cord-311035-s3tkbh9r 28 1 This this DT cord-311035-s3tkbh9r 28 2 Special Special NNP cord-311035-s3tkbh9r 28 3 Report Report NNP cord-311035-s3tkbh9r 28 4 summarizes summarize VBZ cord-311035-s3tkbh9r 28 5 the the DT cord-311035-s3tkbh9r 28 6 two two CD cord-311035-s3tkbh9r 28 7 studies study NNS cord-311035-s3tkbh9r 28 8 with with IN cord-311035-s3tkbh9r 28 9 a a DT cord-311035-s3tkbh9r 28 10 focus focus NN cord-311035-s3tkbh9r 28 11 on on IN cord-311035-s3tkbh9r 28 12 experimental experimental JJ cord-311035-s3tkbh9r 28 13 details detail NNS cord-311035-s3tkbh9r 28 14 and and CC cord-311035-s3tkbh9r 28 15 caveats caveat NNS cord-311035-s3tkbh9r 28 16 that that WDT cord-311035-s3tkbh9r 28 17 will will MD cord-311035-s3tkbh9r 28 18 be be VB cord-311035-s3tkbh9r 28 19 unfamiliar unfamiliar JJ cord-311035-s3tkbh9r 28 20 to to IN cord-311035-s3tkbh9r 28 21 those those DT cord-311035-s3tkbh9r 28 22 outside outside IN cord-311035-s3tkbh9r 28 23 the the DT cord-311035-s3tkbh9r 28 24 deep deep JJ cord-311035-s3tkbh9r 28 25 mutational mutational JJ cord-311035-s3tkbh9r 28 26 scanning scanning NN cord-311035-s3tkbh9r 28 27 community community NN cord-311035-s3tkbh9r 28 28 . . . cord-311035-s3tkbh9r 29 1 Two two CD cord-311035-s3tkbh9r 29 2 deep deep JJ cord-311035-s3tkbh9r 29 3 mutagenesis mutagenesis NN cord-311035-s3tkbh9r 29 4 studies study NNS cord-311035-s3tkbh9r 29 5 have have VBP cord-311035-s3tkbh9r 29 6 determined determine VBN cord-311035-s3tkbh9r 29 7 how how WRB cord-311035-s3tkbh9r 29 8 thousands thousand NNS cord-311035-s3tkbh9r 29 9 of of IN cord-311035-s3tkbh9r 29 10 mutations mutation NNS cord-311035-s3tkbh9r 29 11 within within IN cord-311035-s3tkbh9r 29 12 the the DT cord-311035-s3tkbh9r 29 13 SARS SARS NNP cord-311035-s3tkbh9r 29 14 - - HYPH cord-311035-s3tkbh9r 29 15 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 29 16 spike spike NN cord-311035-s3tkbh9r 29 17 or or CC cord-311035-s3tkbh9r 29 18 the the DT cord-311035-s3tkbh9r 29 19 virus virus NN cord-311035-s3tkbh9r 29 20 ' ' POS cord-311035-s3tkbh9r 29 21 human human JJ cord-311035-s3tkbh9r 29 22 receptor receptor NN cord-311035-s3tkbh9r 29 23 affect affect VBP cord-311035-s3tkbh9r 29 24 their -PRON- PRP$ cord-311035-s3tkbh9r 29 25 binding binding NN cord-311035-s3tkbh9r 29 26 . . . cord-311035-s3tkbh9r 30 1 The the DT cord-311035-s3tkbh9r 30 2 data datum NNS cord-311035-s3tkbh9r 30 3 have have VBP cord-311035-s3tkbh9r 30 4 proven prove VBN cord-311035-s3tkbh9r 30 5 invaluable invaluable JJ cord-311035-s3tkbh9r 30 6 for for IN cord-311035-s3tkbh9r 30 7 engineering engineer VBG cord-311035-s3tkbh9r 30 8 high high JJ cord-311035-s3tkbh9r 30 9 affinity affinity NN cord-311035-s3tkbh9r 30 10 decoy decoy NN cord-311035-s3tkbh9r 30 11 receptors receptor NNS cord-311035-s3tkbh9r 30 12 that that WDT cord-311035-s3tkbh9r 30 13 are be VBP cord-311035-s3tkbh9r 30 14 under under IN cord-311035-s3tkbh9r 30 15 preclinical preclinical JJ cord-311035-s3tkbh9r 30 16 development development NN cord-311035-s3tkbh9r 30 17 as as IN cord-311035-s3tkbh9r 30 18 a a DT cord-311035-s3tkbh9r 30 19 COVID-19 COVID-19 NNP cord-311035-s3tkbh9r 30 20 therapy therapy NN cord-311035-s3tkbh9r 30 21 , , , cord-311035-s3tkbh9r 30 22 and and CC cord-311035-s3tkbh9r 30 23 have have VBP cord-311035-s3tkbh9r 30 24 revealed reveal VBN cord-311035-s3tkbh9r 30 25 the the DT cord-311035-s3tkbh9r 30 26 scope scope NN cord-311035-s3tkbh9r 30 27 of of IN cord-311035-s3tkbh9r 30 28 mutational mutational JJ cord-311035-s3tkbh9r 30 29 tolerance tolerance NN cord-311035-s3tkbh9r 30 30 within within IN cord-311035-s3tkbh9r 30 31 the the DT cord-311035-s3tkbh9r 30 32 spike spike NN cord-311035-s3tkbh9r 30 33 that that WDT cord-311035-s3tkbh9r 30 34 may may MD cord-311035-s3tkbh9r 30 35 have have VB cord-311035-s3tkbh9r 30 36 bearing bear VBG cord-311035-s3tkbh9r 30 37 on on IN cord-311035-s3tkbh9r 30 38 genetic genetic JJ cord-311035-s3tkbh9r 30 39 drift drift NN cord-311035-s3tkbh9r 30 40 as as IN cord-311035-s3tkbh9r 30 41 the the DT cord-311035-s3tkbh9r 30 42 virus virus NN cord-311035-s3tkbh9r 30 43 becomes become VBZ cord-311035-s3tkbh9r 30 44 endemic endemic JJ cord-311035-s3tkbh9r 30 45 and and CC cord-311035-s3tkbh9r 30 46 changes change NNS cord-311035-s3tkbh9r 30 47 over over IN cord-311035-s3tkbh9r 30 48 time time NN cord-311035-s3tkbh9r 30 49 . . . cord-311035-s3tkbh9r 31 1 While while IN cord-311035-s3tkbh9r 31 2 these these DT cord-311035-s3tkbh9r 31 3 two two CD cord-311035-s3tkbh9r 31 4 studies study NNS cord-311035-s3tkbh9r 31 5 focused focus VBD cord-311035-s3tkbh9r 31 6 on on IN cord-311035-s3tkbh9r 31 7 expression expression NN cord-311035-s3tkbh9r 31 8 and and CC cord-311035-s3tkbh9r 31 9 binding binding NN cord-311035-s3tkbh9r 31 10 between between IN cord-311035-s3tkbh9r 31 11 the the DT cord-311035-s3tkbh9r 31 12 viral viral JJ cord-311035-s3tkbh9r 31 13 spike spike NN cord-311035-s3tkbh9r 31 14 and and CC cord-311035-s3tkbh9r 31 15 its -PRON- PRP$ cord-311035-s3tkbh9r 31 16 receptor receptor NN cord-311035-s3tkbh9r 31 17 , , , cord-311035-s3tkbh9r 31 18 the the DT cord-311035-s3tkbh9r 31 19 underlying underlie VBG cord-311035-s3tkbh9r 31 20 selection selection NN cord-311035-s3tkbh9r 31 21 strategies strategy NNS cord-311035-s3tkbh9r 31 22 used use VBN cord-311035-s3tkbh9r 31 23 in in IN cord-311035-s3tkbh9r 31 24 deep deep JJ cord-311035-s3tkbh9r 31 25 mutational mutational JJ cord-311035-s3tkbh9r 31 26 scans scan NNS cord-311035-s3tkbh9r 31 27 are be VBP cord-311035-s3tkbh9r 31 28 increasingly increasingly RB cord-311035-s3tkbh9r 31 29 tied tie VBN cord-311035-s3tkbh9r 31 30 to to IN cord-311035-s3tkbh9r 31 31 more more JJR cord-311035-s3tkbh9r 31 32 complex complex JJ cord-311035-s3tkbh9r 31 33 phenotypes phenotype NNS cord-311035-s3tkbh9r 31 34 , , , cord-311035-s3tkbh9r 31 35 such such JJ cord-311035-s3tkbh9r 31 36 as as IN cord-311035-s3tkbh9r 31 37 selections selection NNS cord-311035-s3tkbh9r 31 38 for for IN cord-311035-s3tkbh9r 31 39 structural structural JJ cord-311035-s3tkbh9r 31 40 stability stability NN cord-311035-s3tkbh9r 31 41 based base VBN cord-311035-s3tkbh9r 31 42 on on IN cord-311035-s3tkbh9r 31 43 protease protease NN cord-311035-s3tkbh9r 31 44 - - HYPH cord-311035-s3tkbh9r 31 45 sensitivity sensitivity NN cord-311035-s3tkbh9r 31 46 [ [ -LRB- cord-311035-s3tkbh9r 31 47 16 16 CD cord-311035-s3tkbh9r 31 48 ] ] -RRB- cord-311035-s3tkbh9r 31 49 , , , cord-311035-s3tkbh9r 31 50 using use VBG cord-311035-s3tkbh9r 31 51 competing compete VBG cord-311035-s3tkbh9r 31 52 ligands ligand NNS cord-311035-s3tkbh9r 31 53 to to TO cord-311035-s3tkbh9r 31 54 engineer engineer VB cord-311035-s3tkbh9r 31 55 specificity specificity NN cord-311035-s3tkbh9r 31 56 into into IN cord-311035-s3tkbh9r 31 57 proteins protein NNS cord-311035-s3tkbh9r 31 58 including include VBG cord-311035-s3tkbh9r 31 59 viral viral JJ cord-311035-s3tkbh9r 31 60 receptors receptor NNS cord-311035-s3tkbh9r 31 61 [ [ -LRB- cord-311035-s3tkbh9r 31 62 17 17 CD cord-311035-s3tkbh9r 31 63 ] ] -RRB- cord-311035-s3tkbh9r 31 64 [ [ -LRB- cord-311035-s3tkbh9r 31 65 18 18 CD cord-311035-s3tkbh9r 31 66 ] ] -RRB- cord-311035-s3tkbh9r 31 67 [ [ -LRB- cord-311035-s3tkbh9r 31 68 19 19 CD cord-311035-s3tkbh9r 31 69 ] ] -RRB- cord-311035-s3tkbh9r 31 70 , , , cord-311035-s3tkbh9r 31 71 and and CC cord-311035-s3tkbh9r 31 72 selections selection NNS cord-311035-s3tkbh9r 31 73 based base VBN cord-311035-s3tkbh9r 31 74 on on IN cord-311035-s3tkbh9r 31 75 catalytic catalytic JJ cord-311035-s3tkbh9r 31 76 or or CC cord-311035-s3tkbh9r 31 77 biological biological JJ cord-311035-s3tkbh9r 31 78 activity activity NN cord-311035-s3tkbh9r 31 79 [ [ -LRB- cord-311035-s3tkbh9r 31 80 20 20 CD cord-311035-s3tkbh9r 31 81 ] ] -RRB- cord-311035-s3tkbh9r 31 82 [ [ -LRB- cord-311035-s3tkbh9r 31 83 21 21 CD cord-311035-s3tkbh9r 31 84 ] ] -RRB- cord-311035-s3tkbh9r 32 1 [ [ -LRB- cord-311035-s3tkbh9r 32 2 22 22 CD cord-311035-s3tkbh9r 32 3 ] ] -RRB- cord-311035-s3tkbh9r 32 4 [ [ -LRB- cord-311035-s3tkbh9r 32 5 23 23 CD cord-311035-s3tkbh9r 32 6 ] ] -RRB- cord-311035-s3tkbh9r 32 7 . . . cord-311035-s3tkbh9r 33 1 Undoubtedly undoubtedly RB cord-311035-s3tkbh9r 33 2 there there EX cord-311035-s3tkbh9r 33 3 are be VBP cord-311035-s3tkbh9r 33 4 more more JJR cord-311035-s3tkbh9r 33 5 questions question NNS cord-311035-s3tkbh9r 33 6 related relate VBN cord-311035-s3tkbh9r 33 7 to to IN cord-311035-s3tkbh9r 33 8 SARS SARS NNP cord-311035-s3tkbh9r 33 9 - - HYPH cord-311035-s3tkbh9r 33 10 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 33 11 biology biology NN cord-311035-s3tkbh9r 33 12 and and CC cord-311035-s3tkbh9r 33 13 the the DT cord-311035-s3tkbh9r 33 14 biochemistry biochemistry NN cord-311035-s3tkbh9r 33 15 of of IN cord-311035-s3tkbh9r 33 16 its -PRON- PRP$ cord-311035-s3tkbh9r 34 1 While while IN cord-311035-s3tkbh9r 34 2 much much JJ cord-311035-s3tkbh9r 34 3 attention attention NN cord-311035-s3tkbh9r 34 4 has have VBZ cord-311035-s3tkbh9r 34 5 been be VBN cord-311035-s3tkbh9r 34 6 given give VBN cord-311035-s3tkbh9r 34 7 to to IN cord-311035-s3tkbh9r 34 8 isolating isolate VBG cord-311035-s3tkbh9r 34 9 monoclonal monoclonal JJ cord-311035-s3tkbh9r 34 10 antibodies antibody NNS cord-311035-s3tkbh9r 34 11 with with IN cord-311035-s3tkbh9r 34 12 tight tight JJ cord-311035-s3tkbh9r 34 13 affinity affinity NN cord-311035-s3tkbh9r 34 14 for for IN cord-311035-s3tkbh9r 34 15 the the DT cord-311035-s3tkbh9r 34 16 SARS SARS NNP cord-311035-s3tkbh9r 34 17 - - HYPH cord-311035-s3tkbh9r 34 18 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 34 19 spike spike NN cord-311035-s3tkbh9r 34 20 ( ( -LRB- cord-311035-s3tkbh9r 34 21 S s NN cord-311035-s3tkbh9r 34 22 ) ) -RRB- cord-311035-s3tkbh9r 34 23 glycoprotein glycoprotein NN cord-311035-s3tkbh9r 34 24 [ [ -LRB- cord-311035-s3tkbh9r 34 25 24 24 CD cord-311035-s3tkbh9r 34 26 ] ] -RRB- cord-311035-s3tkbh9r 34 27 [ [ -LRB- cord-311035-s3tkbh9r 34 28 25 25 CD cord-311035-s3tkbh9r 34 29 ] ] -RRB- cord-311035-s3tkbh9r 34 30 [ [ -LRB- cord-311035-s3tkbh9r 34 31 26 26 CD cord-311035-s3tkbh9r 34 32 ] ] -RRB- cord-311035-s3tkbh9r 34 33 [ [ -LRB- cord-311035-s3tkbh9r 34 34 27 27 CD cord-311035-s3tkbh9r 34 35 ] ] -RRB- cord-311035-s3tkbh9r 34 36 [ [ -LRB- cord-311035-s3tkbh9r 34 37 28 28 CD cord-311035-s3tkbh9r 34 38 ] ] -RRB- cord-311035-s3tkbh9r 34 39 [ [ -LRB- cord-311035-s3tkbh9r 34 40 29 29 CD cord-311035-s3tkbh9r 34 41 ] ] -RRB- cord-311035-s3tkbh9r 34 42 [ [ -LRB- cord-311035-s3tkbh9r 34 43 30 30 CD cord-311035-s3tkbh9r 34 44 ] ] -RRB- cord-311035-s3tkbh9r 34 45 , , , cord-311035-s3tkbh9r 34 46 an an DT cord-311035-s3tkbh9r 34 47 alternative alternative NN cord-311035-s3tkbh9r 34 48 is be VBZ cord-311035-s3tkbh9r 34 49 to to TO cord-311035-s3tkbh9r 34 50 use use VB cord-311035-s3tkbh9r 34 51 the the DT cord-311035-s3tkbh9r 34 52 entry entry NN cord-311035-s3tkbh9r 34 53 receptor receptor NN cord-311035-s3tkbh9r 34 54 as as IN cord-311035-s3tkbh9r 34 55 a a DT cord-311035-s3tkbh9r 34 56 soluble soluble JJ cord-311035-s3tkbh9r 34 57 decoy decoy NN cord-311035-s3tkbh9r 34 58 to to TO cord-311035-s3tkbh9r 34 59 neutralize neutralize VB cord-311035-s3tkbh9r 34 60 infection infection NN cord-311035-s3tkbh9r 34 61 . . . cord-311035-s3tkbh9r 35 1 S S NNP cord-311035-s3tkbh9r 35 2 is be VBZ cord-311035-s3tkbh9r 35 3 a a DT cord-311035-s3tkbh9r 35 4 class class NN cord-311035-s3tkbh9r 36 1 I -PRON- PRP cord-311035-s3tkbh9r 36 2 viral viral JJ cord-311035-s3tkbh9r 36 3 fusion fusion NN cord-311035-s3tkbh9r 36 4 protein protein NN cord-311035-s3tkbh9r 36 5 that that WDT cord-311035-s3tkbh9r 36 6 is be VBZ cord-311035-s3tkbh9r 36 7 proteolytically proteolytically RB cord-311035-s3tkbh9r 36 8 processed process VBN cord-311035-s3tkbh9r 36 9 into into IN cord-311035-s3tkbh9r 36 10 two two CD cord-311035-s3tkbh9r 36 11 subunits subunit NNS cord-311035-s3tkbh9r 36 12 , , , cord-311035-s3tkbh9r 36 13 S1 S1 NNP cord-311035-s3tkbh9r 36 14 and and CC cord-311035-s3tkbh9r 36 15 S2 S2 NNP cord-311035-s3tkbh9r 36 16 , , , cord-311035-s3tkbh9r 36 17 that that WDT cord-311035-s3tkbh9r 36 18 are be VBP cord-311035-s3tkbh9r 36 19 non non JJ cord-311035-s3tkbh9r 36 20 - - JJ cord-311035-s3tkbh9r 36 21 covalently covalently RB cord-311035-s3tkbh9r 36 22 associated associate VBN cord-311035-s3tkbh9r 36 23 and and CC cord-311035-s3tkbh9r 36 24 decorate decorate VB cord-311035-s3tkbh9r 36 25 the the DT cord-311035-s3tkbh9r 36 26 coronavirus coronavirus NN cord-311035-s3tkbh9r 36 27 envelope envelope NN cord-311035-s3tkbh9r 36 28 [ [ -LRB- cord-311035-s3tkbh9r 36 29 31 31 CD cord-311035-s3tkbh9r 36 30 ] ] -RRB- cord-311035-s3tkbh9r 37 1 [ [ -LRB- cord-311035-s3tkbh9r 37 2 32 32 CD cord-311035-s3tkbh9r 37 3 ] ] -RRB- cord-311035-s3tkbh9r 37 4 [ [ -LRB- cord-311035-s3tkbh9r 37 5 33 33 CD cord-311035-s3tkbh9r 37 6 ] ] -RRB- cord-311035-s3tkbh9r 37 7 . . . cord-311035-s3tkbh9r 38 1 S S NNP cord-311035-s3tkbh9r 38 2 recognizes recognize VBZ cord-311035-s3tkbh9r 38 3 angiotensin angiotensin NN cord-311035-s3tkbh9r 38 4 - - HYPH cord-311035-s3tkbh9r 38 5 converting convert VBG cord-311035-s3tkbh9r 38 6 enzyme enzyme NN cord-311035-s3tkbh9r 38 7 2 2 CD cord-311035-s3tkbh9r 38 8 ( ( -LRB- cord-311035-s3tkbh9r 38 9 ACE2 ACE2 NNP cord-311035-s3tkbh9r 38 10 ) ) -RRB- cord-311035-s3tkbh9r 38 11 on on IN cord-311035-s3tkbh9r 38 12 host host NN cord-311035-s3tkbh9r 38 13 cells cell NNS cord-311035-s3tkbh9r 38 14 to to TO cord-311035-s3tkbh9r 38 15 initiate initiate VB cord-311035-s3tkbh9r 38 16 attachment attachment NN cord-311035-s3tkbh9r 38 17 and and CC cord-311035-s3tkbh9r 38 18 fusion fusion NN cord-311035-s3tkbh9r 38 19 of of IN cord-311035-s3tkbh9r 38 20 the the DT cord-311035-s3tkbh9r 38 21 viral viral JJ cord-311035-s3tkbh9r 38 22 and and CC cord-311035-s3tkbh9r 38 23 plasma plasma NN cord-311035-s3tkbh9r 38 24 membranes membrane NNS cord-311035-s3tkbh9r 38 25 [ [ -LRB- cord-311035-s3tkbh9r 38 26 33 33 CD cord-311035-s3tkbh9r 38 27 ] ] -RRB- cord-311035-s3tkbh9r 38 28 [ [ -LRB- cord-311035-s3tkbh9r 38 29 34 34 CD cord-311035-s3tkbh9r 38 30 ] ] -RRB- cord-311035-s3tkbh9r 38 31 [ [ -LRB- cord-311035-s3tkbh9r 38 32 35 35 CD cord-311035-s3tkbh9r 38 33 ] ] -RRB- cord-311035-s3tkbh9r 38 34 [ [ -LRB- cord-311035-s3tkbh9r 38 35 36 36 CD cord-311035-s3tkbh9r 38 36 ] ] -RRB- cord-311035-s3tkbh9r 38 37 [ [ -LRB- cord-311035-s3tkbh9r 38 38 37 37 CD cord-311035-s3tkbh9r 38 39 ] ] -RRB- cord-311035-s3tkbh9r 38 40 [ [ -LRB- cord-311035-s3tkbh9r 38 41 38 38 CD cord-311035-s3tkbh9r 38 42 ] ] -RRB- cord-311035-s3tkbh9r 38 43 . . . cord-311035-s3tkbh9r 39 1 Soluble soluble JJ cord-311035-s3tkbh9r 39 2 ACE2 ACE2 NNP cord-311035-s3tkbh9r 39 3 ( ( -LRB- cord-311035-s3tkbh9r 39 4 sACE2 sACE2 NNP cord-311035-s3tkbh9r 39 5 ) ) -RRB- cord-311035-s3tkbh9r 39 6 blocks block VBZ cord-311035-s3tkbh9r 39 7 receptor receptor NN cord-311035-s3tkbh9r 39 8 - - HYPH cord-311035-s3tkbh9r 39 9 binding bind VBG cord-311035-s3tkbh9r 39 10 sites site NNS cord-311035-s3tkbh9r 39 11 on on IN cord-311035-s3tkbh9r 39 12 S S NNP cord-311035-s3tkbh9r 39 13 [ [ -LRB- cord-311035-s3tkbh9r 39 14 15 15 CD cord-311035-s3tkbh9r 39 15 , , , cord-311035-s3tkbh9r 39 16 37 37 CD cord-311035-s3tkbh9r 39 17 , , , cord-311035-s3tkbh9r 39 18 [ [ -LRB- cord-311035-s3tkbh9r 39 19 39 39 CD cord-311035-s3tkbh9r 39 20 ] ] -RRB- cord-311035-s3tkbh9r 39 21 [ [ -LRB- cord-311035-s3tkbh9r 39 22 40 40 CD cord-311035-s3tkbh9r 39 23 ] ] -RRB- cord-311035-s3tkbh9r 39 24 [ [ -LRB- cord-311035-s3tkbh9r 39 25 41 41 CD cord-311035-s3tkbh9r 39 26 ] ] -RRB- cord-311035-s3tkbh9r 39 27 [ [ -LRB- cord-311035-s3tkbh9r 39 28 42 42 CD cord-311035-s3tkbh9r 39 29 ] ] -RRB- cord-311035-s3tkbh9r 39 30 and and CC cord-311035-s3tkbh9r 39 31 while while IN cord-311035-s3tkbh9r 39 32 escape escape NN cord-311035-s3tkbh9r 39 33 mutations mutation NNS cord-311035-s3tkbh9r 39 34 in in IN cord-311035-s3tkbh9r 39 35 S S NNP cord-311035-s3tkbh9r 39 36 rapidly rapidly RB cord-311035-s3tkbh9r 39 37 emerge emerge VBP cord-311035-s3tkbh9r 39 38 in in IN cord-311035-s3tkbh9r 39 39 tissue tissue NN cord-311035-s3tkbh9r 39 40 culture culture NN cord-311035-s3tkbh9r 39 41 in in IN cord-311035-s3tkbh9r 39 42 the the DT cord-311035-s3tkbh9r 39 43 presence presence NN cord-311035-s3tkbh9r 39 44 of of IN cord-311035-s3tkbh9r 39 45 monoclonal monoclonal JJ cord-311035-s3tkbh9r 39 46 antibodies antibody NNS cord-311035-s3tkbh9r 39 47 [ [ -LRB- cord-311035-s3tkbh9r 39 48 43 43 CD cord-311035-s3tkbh9r 39 49 ] ] -RRB- cord-311035-s3tkbh9r 39 50 , , . cord-311035-s3tkbh9r 40 1 in in IN cord-311035-s3tkbh9r 40 2 principle principle NN cord-311035-s3tkbh9r 40 3 the the DT cord-311035-s3tkbh9r 40 4 virus virus NN cord-311035-s3tkbh9r 40 5 has have VBZ cord-311035-s3tkbh9r 40 6 limited limit VBN cord-311035-s3tkbh9r 40 7 mechanisms mechanism NNS cord-311035-s3tkbh9r 40 8 to to TO cord-311035-s3tkbh9r 40 9 escape escape VB cord-311035-s3tkbh9r 40 10 a a DT cord-311035-s3tkbh9r 40 11 soluble soluble JJ cord-311035-s3tkbh9r 40 12 decoy decoy NN cord-311035-s3tkbh9r 40 13 receptor receptor NN cord-311035-s3tkbh9r 40 14 without without IN cord-311035-s3tkbh9r 40 15 simultaneously simultaneously RB cord-311035-s3tkbh9r 40 16 losing lose VBG cord-311035-s3tkbh9r 40 17 affinity affinity NN cord-311035-s3tkbh9r 40 18 for for IN cord-311035-s3tkbh9r 40 19 the the DT cord-311035-s3tkbh9r 40 20 natural natural JJ cord-311035-s3tkbh9r 40 21 receptor receptor NN cord-311035-s3tkbh9r 40 22 . . . cord-311035-s3tkbh9r 41 1 The the DT cord-311035-s3tkbh9r 41 2 decoy decoy NN cord-311035-s3tkbh9r 41 3 receptor receptor NN cord-311035-s3tkbh9r 41 4 might may MD cord-311035-s3tkbh9r 41 5 also also RB cord-311035-s3tkbh9r 41 6 have have VB cord-311035-s3tkbh9r 41 7 a a DT cord-311035-s3tkbh9r 41 8 virucidal virucidal JJ cord-311035-s3tkbh9r 41 9 effect effect NN cord-311035-s3tkbh9r 41 10 by by IN cord-311035-s3tkbh9r 41 11 inducing induce VBG cord-311035-s3tkbh9r 41 12 conformational conformational JJ cord-311035-s3tkbh9r 41 13 changes change NNS cord-311035-s3tkbh9r 41 14 and and CC cord-311035-s3tkbh9r 41 15 S1 s1 NN cord-311035-s3tkbh9r 41 16 shedding shedding NN cord-311035-s3tkbh9r 41 17 , , , cord-311035-s3tkbh9r 41 18 such such JJ cord-311035-s3tkbh9r 41 19 that that IN cord-311035-s3tkbh9r 41 20 virus virus NN cord-311035-s3tkbh9r 41 21 particles particle NNS cord-311035-s3tkbh9r 41 22 are be VBP cord-311035-s3tkbh9r 41 23 inactivated inactivate VBN cord-311035-s3tkbh9r 41 24 even even RB cord-311035-s3tkbh9r 41 25 if if IN cord-311035-s3tkbh9r 41 26 sACE2 sACE2 NNP cord-311035-s3tkbh9r 41 27 dissociates dissociate VBZ cord-311035-s3tkbh9r 41 28 . . . cord-311035-s3tkbh9r 42 1 However however RB cord-311035-s3tkbh9r 42 2 , , , cord-311035-s3tkbh9r 42 3 monoclonal monoclonal JJ cord-311035-s3tkbh9r 42 4 antibodies antibody NNS cord-311035-s3tkbh9r 42 5 have have VBP cord-311035-s3tkbh9r 42 6 superior superior JJ cord-311035-s3tkbh9r 42 7 affinity affinity NN cord-311035-s3tkbh9r 42 8 and and CC cord-311035-s3tkbh9r 42 9 neutralization neutralization NN cord-311035-s3tkbh9r 42 10 efficacy efficacy NN cord-311035-s3tkbh9r 42 11 . . . cord-311035-s3tkbh9r 43 1 To to TO cord-311035-s3tkbh9r 43 2 improve improve VB cord-311035-s3tkbh9r 43 3 the the DT cord-311035-s3tkbh9r 43 4 therapeutic therapeutic JJ cord-311035-s3tkbh9r 43 5 potential potential NN cord-311035-s3tkbh9r 43 6 of of IN cord-311035-s3tkbh9r 43 7 decoy decoy NN cord-311035-s3tkbh9r 43 8 receptors receptor NNS cord-311035-s3tkbh9r 43 9 , , , cord-311035-s3tkbh9r 43 10 my -PRON- PRP$ cord-311035-s3tkbh9r 43 11 group group NN cord-311035-s3tkbh9r 43 12 used use VBD cord-311035-s3tkbh9r 43 13 deep deep JJ cord-311035-s3tkbh9r 43 14 mutagenesis mutagenesis NN cord-311035-s3tkbh9r 43 15 to to TO cord-311035-s3tkbh9r 43 16 find find VB cord-311035-s3tkbh9r 43 17 mutations mutation NNS cord-311035-s3tkbh9r 43 18 in in IN cord-311035-s3tkbh9r 43 19 ACE2 ACE2 NNP cord-311035-s3tkbh9r 43 20 that that WDT cord-311035-s3tkbh9r 43 21 enhance enhance VBP cord-311035-s3tkbh9r 43 22 affinity affinity NN cord-311035-s3tkbh9r 43 23 [ [ -LRB- cord-311035-s3tkbh9r 43 24 15 15 CD cord-311035-s3tkbh9r 43 25 ] ] -RRB- cord-311035-s3tkbh9r 43 26 . . . cord-311035-s3tkbh9r 44 1 A a DT cord-311035-s3tkbh9r 44 2 library library NN cord-311035-s3tkbh9r 44 3 of of IN cord-311035-s3tkbh9r 44 4 over over IN cord-311035-s3tkbh9r 44 5 2,000 2,000 CD cord-311035-s3tkbh9r 44 6 single single JJ cord-311035-s3tkbh9r 44 7 amino amino NN cord-311035-s3tkbh9r 44 8 acid acid NN cord-311035-s3tkbh9r 44 9 substitutions substitution NNS cord-311035-s3tkbh9r 44 10 in in IN cord-311035-s3tkbh9r 44 11 ACE2 ACE2 NNP cord-311035-s3tkbh9r 44 12 was be VBD cord-311035-s3tkbh9r 44 13 constructed construct VBN cord-311035-s3tkbh9r 44 14 , , , cord-311035-s3tkbh9r 44 15 focused focus VBN cord-311035-s3tkbh9r 44 16 on on IN cord-311035-s3tkbh9r 44 17 diversification diversification NN cord-311035-s3tkbh9r 44 18 of of IN cord-311035-s3tkbh9r 44 19 residues residue NNS cord-311035-s3tkbh9r 44 20 at at IN cord-311035-s3tkbh9r 44 21 the the DT cord-311035-s3tkbh9r 44 22 structurally structurally RB cord-311035-s3tkbh9r 44 23 defined define VBN cord-311035-s3tkbh9r 44 24 interface interface NN cord-311035-s3tkbh9r 44 25 with with IN cord-311035-s3tkbh9r 44 26 the the DT cord-311035-s3tkbh9r 44 27 receptor receptor NN cord-311035-s3tkbh9r 44 28 - - HYPH cord-311035-s3tkbh9r 44 29 binding bind VBG cord-311035-s3tkbh9r 44 30 domain domain NN cord-311035-s3tkbh9r 44 31 ( ( -LRB- cord-311035-s3tkbh9r 44 32 RBD RBD NNP cord-311035-s3tkbh9r 44 33 ) ) -RRB- cord-311035-s3tkbh9r 44 34 of of IN cord-311035-s3tkbh9r 44 35 S S NNP cord-311035-s3tkbh9r 44 36 [ [ -LRB- cord-311035-s3tkbh9r 44 37 44 44 CD cord-311035-s3tkbh9r 44 38 , , , cord-311035-s3tkbh9r 44 39 45 45 CD cord-311035-s3tkbh9r 44 40 ] ] -RRB- cord-311035-s3tkbh9r 44 41 and and CC cord-311035-s3tkbh9r 44 42 also also RB cord-311035-s3tkbh9r 44 43 within within IN cord-311035-s3tkbh9r 44 44 the the DT cord-311035-s3tkbh9r 44 45 ACE2 ACE2 NNP cord-311035-s3tkbh9r 44 46 catalytic catalytic JJ cord-311035-s3tkbh9r 44 47 cleft cleft NN cord-311035-s3tkbh9r 44 48 . . . cord-311035-s3tkbh9r 45 1 The the DT cord-311035-s3tkbh9r 45 2 library library NN cord-311035-s3tkbh9r 45 3 was be VBD cord-311035-s3tkbh9r 45 4 expressed express VBN cord-311035-s3tkbh9r 45 5 in in IN cord-311035-s3tkbh9r 45 6 a a DT cord-311035-s3tkbh9r 45 7 human human JJ cord-311035-s3tkbh9r 45 8 cell cell NN cord-311035-s3tkbh9r 45 9 line line NN cord-311035-s3tkbh9r 45 10 , , , cord-311035-s3tkbh9r 45 11 with with IN cord-311035-s3tkbh9r 45 12 a a DT cord-311035-s3tkbh9r 45 13 c c NNP cord-311035-s3tkbh9r 45 14 - - HYPH cord-311035-s3tkbh9r 45 15 myc myc NNP cord-311035-s3tkbh9r 45 16 epitope epitope NN cord-311035-s3tkbh9r 45 17 tag tag NN cord-311035-s3tkbh9r 45 18 fused fuse VBN cord-311035-s3tkbh9r 45 19 to to IN cord-311035-s3tkbh9r 45 20 the the DT cord-311035-s3tkbh9r 45 21 extracellular extracellular JJ cord-311035-s3tkbh9r 45 22 N n CD cord-311035-s3tkbh9r 45 23 - - HYPH cord-311035-s3tkbh9r 45 24 terminus terminus NN cord-311035-s3tkbh9r 45 25 of of IN cord-311035-s3tkbh9r 45 26 ACE2 ACE2 NNP cord-311035-s3tkbh9r 45 27 for for IN cord-311035-s3tkbh9r 45 28 detection detection NN cord-311035-s3tkbh9r 45 29 of of IN cord-311035-s3tkbh9r 45 30 surface surface NN cord-311035-s3tkbh9r 45 31 expressed express VBD cord-311035-s3tkbh9r 45 32 protein protein NN cord-311035-s3tkbh9r 45 33 . . . cord-311035-s3tkbh9r 46 1 Other other JJ cord-311035-s3tkbh9r 46 2 than than IN cord-311035-s3tkbh9r 46 3 the the DT cord-311035-s3tkbh9r 46 4 presence presence NN cord-311035-s3tkbh9r 46 5 of of IN cord-311035-s3tkbh9r 46 6 the the DT cord-311035-s3tkbh9r 46 7 epitope epitope NN cord-311035-s3tkbh9r 46 8 tag tag NN cord-311035-s3tkbh9r 46 9 , , , cord-311035-s3tkbh9r 46 10 ACE2 ACE2 NNP cord-311035-s3tkbh9r 46 11 expressed express VBD cord-311035-s3tkbh9r 46 12 in in IN cord-311035-s3tkbh9r 46 13 this this DT cord-311035-s3tkbh9r 46 14 experimental experimental JJ cord-311035-s3tkbh9r 46 15 selection selection NN cord-311035-s3tkbh9r 46 16 system system NN cord-311035-s3tkbh9r 46 17 matches match VBZ cord-311035-s3tkbh9r 46 18 native native JJ cord-311035-s3tkbh9r 46 19 ACE2 ACE2 NNP cord-311035-s3tkbh9r 46 20 in in IN cord-311035-s3tkbh9r 46 21 the the DT cord-311035-s3tkbh9r 46 22 human human JJ cord-311035-s3tkbh9r 46 23 body body NN cord-311035-s3tkbh9r 46 24 . . . cord-311035-s3tkbh9r 47 1 The the DT cord-311035-s3tkbh9r 47 2 culture culture NN cord-311035-s3tkbh9r 47 3 expressing express VBG cord-311035-s3tkbh9r 47 4 the the DT cord-311035-s3tkbh9r 47 5 ACE2 ACE2 NNP cord-311035-s3tkbh9r 47 6 library library NN cord-311035-s3tkbh9r 47 7 was be VBD cord-311035-s3tkbh9r 47 8 then then RB cord-311035-s3tkbh9r 47 9 selected select VBN cord-311035-s3tkbh9r 47 10 by by IN cord-311035-s3tkbh9r 47 11 fluorescence fluorescence NN cord-311035-s3tkbh9r 47 12 activated activate VBN cord-311035-s3tkbh9r 47 13 cell cell NN cord-311035-s3tkbh9r 47 14 sorting sorting NN cord-311035-s3tkbh9r 47 15 ( ( -LRB- cord-311035-s3tkbh9r 47 16 FACS FACS NNP cord-311035-s3tkbh9r 47 17 ) ) -RRB- cord-311035-s3tkbh9r 47 18 to to TO cord-311035-s3tkbh9r 47 19 collect collect VB cord-311035-s3tkbh9r 47 20 cells cell NNS cord-311035-s3tkbh9r 47 21 expressing express VBG cord-311035-s3tkbh9r 47 22 ACE2 ACE2 NNP cord-311035-s3tkbh9r 47 23 variants variant NNS cord-311035-s3tkbh9r 47 24 with with IN cord-311035-s3tkbh9r 47 25 tight tight JJ cord-311035-s3tkbh9r 47 26 affinity affinity NN cord-311035-s3tkbh9r 47 27 for for IN cord-311035-s3tkbh9r 47 28 fluorescently fluorescently RB cord-311035-s3tkbh9r 47 29 labeled label VBN cord-311035-s3tkbh9r 47 30 RBD RBD NNP cord-311035-s3tkbh9r 47 31 from from IN cord-311035-s3tkbh9r 47 32 S S NNP cord-311035-s3tkbh9r 47 33 of of IN cord-311035-s3tkbh9r 47 34 SARS SARS NNP cord-311035-s3tkbh9r 47 35 - - HYPH cord-311035-s3tkbh9r 47 36 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 48 1 ( ( -LRB- cord-311035-s3tkbh9r 48 2 Figure figure NN cord-311035-s3tkbh9r 48 3 1A 1a NN cord-311035-s3tkbh9r 48 4 ) ) -RRB- cord-311035-s3tkbh9r 48 5 . . . cord-311035-s3tkbh9r 49 1 For for IN cord-311035-s3tkbh9r 49 2 the the DT cord-311035-s3tkbh9r 49 3 artificial artificial JJ cord-311035-s3tkbh9r 49 4 selection selection NN cord-311035-s3tkbh9r 49 5 to to TO cord-311035-s3tkbh9r 49 6 be be VB cord-311035-s3tkbh9r 49 7 successful successful JJ cord-311035-s3tkbh9r 49 8 , , , cord-311035-s3tkbh9r 49 9 cells cell NNS cord-311035-s3tkbh9r 49 10 must must MD cord-311035-s3tkbh9r 49 11 express express VB cord-311035-s3tkbh9r 49 12 a a DT cord-311035-s3tkbh9r 49 13 single single JJ cord-311035-s3tkbh9r 49 14 protein protein NN cord-311035-s3tkbh9r 49 15 variant variant NN cord-311035-s3tkbh9r 49 16 from from IN cord-311035-s3tkbh9r 49 17 a a DT cord-311035-s3tkbh9r 49 18 single single JJ cord-311035-s3tkbh9r 49 19 sequence sequence NN cord-311035-s3tkbh9r 49 20 variant variant NN cord-311035-s3tkbh9r 49 21 , , , cord-311035-s3tkbh9r 49 22 thereby thereby RB cord-311035-s3tkbh9r 49 23 providing provide VBG cord-311035-s3tkbh9r 49 24 a a DT cord-311035-s3tkbh9r 49 25 tight tight JJ cord-311035-s3tkbh9r 49 26 physical physical JJ cord-311035-s3tkbh9r 49 27 link link NN cord-311035-s3tkbh9r 49 28 between between IN cord-311035-s3tkbh9r 49 29 the the DT cord-311035-s3tkbh9r 49 30 phenotype phenotype NN cord-311035-s3tkbh9r 49 31 of of IN cord-311035-s3tkbh9r 49 32 ACE2 ACE2 NNP cord-311035-s3tkbh9r 49 33 expressed express VBD cord-311035-s3tkbh9r 49 34 at at IN cord-311035-s3tkbh9r 49 35 the the DT cord-311035-s3tkbh9r 49 36 plasma plasma NN cord-311035-s3tkbh9r 49 37 membrane membrane NN cord-311035-s3tkbh9r 49 38 and and CC cord-311035-s3tkbh9r 49 39 a a DT cord-311035-s3tkbh9r 49 40 single single JJ cord-311035-s3tkbh9r 49 41 sequence sequence NN cord-311035-s3tkbh9r 49 42 within within IN cord-311035-s3tkbh9r 49 43 the the DT cord-311035-s3tkbh9r 49 44 cell cell NN cord-311035-s3tkbh9r 49 45 . . . cord-311035-s3tkbh9r 50 1 Getting get VBG cord-311035-s3tkbh9r 50 2 human human JJ cord-311035-s3tkbh9r 50 3 cells cell NNS cord-311035-s3tkbh9r 50 4 in in IN cord-311035-s3tkbh9r 50 5 culture culture NN cord-311035-s3tkbh9r 50 6 to to TO cord-311035-s3tkbh9r 50 7 acquire acquire VB cord-311035-s3tkbh9r 50 8 and and CC cord-311035-s3tkbh9r 50 9 express express VB cord-311035-s3tkbh9r 50 10 a a DT cord-311035-s3tkbh9r 50 11 single single JJ cord-311035-s3tkbh9r 50 12 coding code VBG cord-311035-s3tkbh9r 50 13 variant variant NN cord-311035-s3tkbh9r 50 14 is be VBZ cord-311035-s3tkbh9r 50 15 no no DT cord-311035-s3tkbh9r 50 16 trivial trivial JJ cord-311035-s3tkbh9r 50 17 feat feat NN cord-311035-s3tkbh9r 50 18 , , , cord-311035-s3tkbh9r 50 19 as as IN cord-311035-s3tkbh9r 50 20 transfection transfection NN cord-311035-s3tkbh9r 50 21 methods method NNS cord-311035-s3tkbh9r 50 22 typically typically RB cord-311035-s3tkbh9r 50 23 introduce introduce VBP cord-311035-s3tkbh9r 50 24 many many JJ cord-311035-s3tkbh9r 50 25 plasmid plasmid NN cord-311035-s3tkbh9r 50 26 copies copy NNS cord-311035-s3tkbh9r 50 27 . . . cord-311035-s3tkbh9r 51 1 Different different JJ cord-311035-s3tkbh9r 51 2 methods method NNS cord-311035-s3tkbh9r 51 3 to to TO cord-311035-s3tkbh9r 51 4 solve solve VB cord-311035-s3tkbh9r 51 5 this this DT cord-311035-s3tkbh9r 51 6 technical technical JJ cord-311035-s3tkbh9r 51 7 challenge challenge NN cord-311035-s3tkbh9r 51 8 have have VBP cord-311035-s3tkbh9r 51 9 included include VBN cord-311035-s3tkbh9r 51 10 the the DT cord-311035-s3tkbh9r 51 11 use use NN cord-311035-s3tkbh9r 51 12 of of IN cord-311035-s3tkbh9r 51 13 episomal episomal JJ cord-311035-s3tkbh9r 51 14 plasmids plasmid NNS cord-311035-s3tkbh9r 51 15 that that WDT cord-311035-s3tkbh9r 51 16 randomly randomly RB cord-311035-s3tkbh9r 51 17 partition partition VBP cord-311035-s3tkbh9r 51 18 to to IN cord-311035-s3tkbh9r 51 19 daughter daughter NN cord-311035-s3tkbh9r 51 20 cells cell NNS cord-311035-s3tkbh9r 51 21 during during IN cord-311035-s3tkbh9r 51 22 division division NN cord-311035-s3tkbh9r 51 23 until until IN cord-311035-s3tkbh9r 51 24 progeny progeny NN cord-311035-s3tkbh9r 51 25 harbor harbor VBP cord-311035-s3tkbh9r 51 26 a a DT cord-311035-s3tkbh9r 51 27 single single JJ cord-311035-s3tkbh9r 51 28 coding code VBG cord-311035-s3tkbh9r 51 29 variant variant NN cord-311035-s3tkbh9r 51 30 over over IN cord-311035-s3tkbh9r 51 31 time time NN cord-311035-s3tkbh9r 51 32 [ [ -LRB- cord-311035-s3tkbh9r 51 33 4 4 CD cord-311035-s3tkbh9r 51 34 ] ] -RRB- cord-311035-s3tkbh9r 51 35 , , , cord-311035-s3tkbh9r 51 36 the the DT cord-311035-s3tkbh9r 51 37 use use NN cord-311035-s3tkbh9r 51 38 of of IN cord-311035-s3tkbh9r 51 39 engineered engineer VBN cord-311035-s3tkbh9r 51 40 integration integration NN cord-311035-s3tkbh9r 51 41 sites site NNS cord-311035-s3tkbh9r 51 42 in in IN cord-311035-s3tkbh9r 51 43 the the DT cord-311035-s3tkbh9r 51 44 genome genome NN cord-311035-s3tkbh9r 51 45 [ [ -LRB- cord-311035-s3tkbh9r 51 46 9 9 CD cord-311035-s3tkbh9r 51 47 , , , cord-311035-s3tkbh9r 51 48 46 46 CD cord-311035-s3tkbh9r 51 49 , , , cord-311035-s3tkbh9r 51 50 47 47 CD cord-311035-s3tkbh9r 51 51 ] ] -RRB- cord-311035-s3tkbh9r 51 52 , , , cord-311035-s3tkbh9r 51 53 or or CC cord-311035-s3tkbh9r 51 54 the the DT cord-311035-s3tkbh9r 51 55 use use NN cord-311035-s3tkbh9r 51 56 of of IN cord-311035-s3tkbh9r 51 57 viral viral JJ cord-311035-s3tkbh9r 51 58 vectors vector NNS cord-311035-s3tkbh9r 51 59 at at IN cord-311035-s3tkbh9r 51 60 low low JJ cord-311035-s3tkbh9r 51 61 multiplicities multiplicity NNS cord-311035-s3tkbh9r 51 62 - - HYPH cord-311035-s3tkbh9r 51 63 of of IN cord-311035-s3tkbh9r 51 64 - - HYPH cord-311035-s3tkbh9r 51 65 infection infection NN cord-311035-s3tkbh9r 51 66 [ [ -LRB- cord-311035-s3tkbh9r 51 67 48 48 CD cord-311035-s3tkbh9r 51 68 , , , cord-311035-s3tkbh9r 51 69 49 49 CD cord-311035-s3tkbh9r 51 70 ] ] -RRB- cord-311035-s3tkbh9r 51 71 . . . cord-311035-s3tkbh9r 52 1 My -PRON- PRP$ cord-311035-s3tkbh9r 52 2 group group NN cord-311035-s3tkbh9r 52 3 used use VBD cord-311035-s3tkbh9r 52 4 carrier carrier NN cord-311035-s3tkbh9r 52 5 DNA DNA NNP cord-311035-s3tkbh9r 52 6 to to TO cord-311035-s3tkbh9r 52 7 sufficiently sufficiently RB cord-311035-s3tkbh9r 52 8 dilute dilute VB cord-311035-s3tkbh9r 52 9 the the DT cord-311035-s3tkbh9r 52 10 ACE2 ACE2 NNP cord-311035-s3tkbh9r 52 11 plasmid plasmid NN cord-311035-s3tkbh9r 52 12 library library NN cord-311035-s3tkbh9r 52 13 such such JJ cord-311035-s3tkbh9r 52 14 that that IN cord-311035-s3tkbh9r 52 15 each each DT cord-311035-s3tkbh9r 52 16 cell cell NN cord-311035-s3tkbh9r 52 17 typically typically RB cord-311035-s3tkbh9r 52 18 acquired acquire VBD cord-311035-s3tkbh9r 52 19 no no DT cord-311035-s3tkbh9r 52 20 more more JJR cord-311035-s3tkbh9r 52 21 than than IN cord-311035-s3tkbh9r 52 22 a a DT cord-311035-s3tkbh9r 52 23 single single JJ cord-311035-s3tkbh9r 52 24 coding code VBG cord-311035-s3tkbh9r 52 25 variant variant NN cord-311035-s3tkbh9r 52 26 [ [ -LRB- cord-311035-s3tkbh9r 52 27 11 11 CD cord-311035-s3tkbh9r 52 28 ] ] -RRB- cord-311035-s3tkbh9r 52 29 . . . cord-311035-s3tkbh9r 53 1 An an DT cord-311035-s3tkbh9r 53 2 episomal episomal JJ cord-311035-s3tkbh9r 53 3 plasmid plasmid NN cord-311035-s3tkbh9r 53 4 is be VBZ cord-311035-s3tkbh9r 53 5 used use VBN cord-311035-s3tkbh9r 53 6 for for IN cord-311035-s3tkbh9r 53 7 the the DT cord-311035-s3tkbh9r 53 8 library library NN cord-311035-s3tkbh9r 53 9 so so IN cord-311035-s3tkbh9r 53 10 that that IN cord-311035-s3tkbh9r 53 11 extrachromosomal extrachromosomal VBN cord-311035-s3tkbh9r 53 12 replication replication NN cord-311035-s3tkbh9r 53 13 within within IN cord-311035-s3tkbh9r 53 14 the the DT cord-311035-s3tkbh9r 53 15 cell cell NN cord-311035-s3tkbh9r 53 16 enhances enhance VBZ cord-311035-s3tkbh9r 53 17 expression expression NN cord-311035-s3tkbh9r 53 18 of of IN cord-311035-s3tkbh9r 53 19 the the DT cord-311035-s3tkbh9r 53 20 protein protein NN cord-311035-s3tkbh9r 53 21 under under IN cord-311035-s3tkbh9r 53 22 investigation investigation NN cord-311035-s3tkbh9r 53 23 . . . cord-311035-s3tkbh9r 54 1 ( ( -LRB- cord-311035-s3tkbh9r 54 2 The the DT cord-311035-s3tkbh9r 54 3 carrier carrier NN cord-311035-s3tkbh9r 54 4 DNA dna NN cord-311035-s3tkbh9r 54 5 , , , cord-311035-s3tkbh9r 54 6 itself -PRON- PRP cord-311035-s3tkbh9r 54 7 a a DT cord-311035-s3tkbh9r 54 8 modified modify VBN cord-311035-s3tkbh9r 54 9 episomal episomal JJ cord-311035-s3tkbh9r 54 10 plasmid plasmid NN cord-311035-s3tkbh9r 54 11 , , , cord-311035-s3tkbh9r 54 12 further further RB cord-311035-s3tkbh9r 54 13 assists assist NNS cord-311035-s3tkbh9r 54 14 in in IN cord-311035-s3tkbh9r 54 15 this this DT cord-311035-s3tkbh9r 54 16 process process NN cord-311035-s3tkbh9r 54 17 [ [ -LRB- cord-311035-s3tkbh9r 54 18 50 50 CD cord-311035-s3tkbh9r 54 19 ] ] -RRB- cord-311035-s3tkbh9r 54 20 . . . cord-311035-s3tkbh9r 54 21 ) ) -RRB- cord-311035-s3tkbh9r 55 1 The the DT cord-311035-s3tkbh9r 55 2 disadvantage disadvantage NN cord-311035-s3tkbh9r 55 3 to to IN cord-311035-s3tkbh9r 55 4 this this DT cord-311035-s3tkbh9r 55 5 simple simple JJ cord-311035-s3tkbh9r 55 6 solution solution NN cord-311035-s3tkbh9r 55 7 for for IN cord-311035-s3tkbh9r 55 8 linking link VBG cord-311035-s3tkbh9r 55 9 a a DT cord-311035-s3tkbh9r 55 10 single single JJ cord-311035-s3tkbh9r 55 11 genotype genotype NN cord-311035-s3tkbh9r 55 12 to to IN cord-311035-s3tkbh9r 55 13 phenotype phenotype NN cord-311035-s3tkbh9r 55 14 is be VBZ cord-311035-s3tkbh9r 55 15 that that IN cord-311035-s3tkbh9r 55 16 the the DT cord-311035-s3tkbh9r 55 17 coding code VBG cord-311035-s3tkbh9r 55 18 sequence sequence NN cord-311035-s3tkbh9r 55 19 is be VBZ cord-311035-s3tkbh9r 55 20 so so RB cord-311035-s3tkbh9r 55 21 diluted dilute VBN cord-311035-s3tkbh9r 55 22 with with IN cord-311035-s3tkbh9r 55 23 carrier carrier NN cord-311035-s3tkbh9r 55 24 DNA dna NN cord-311035-s3tkbh9r 55 25 , , , cord-311035-s3tkbh9r 55 26 most most JJS cord-311035-s3tkbh9r 55 27 cells cell NNS cord-311035-s3tkbh9r 55 28 in in IN cord-311035-s3tkbh9r 55 29 the the DT cord-311035-s3tkbh9r 55 30 ( ( -LRB- cord-311035-s3tkbh9r 55 31 A a NN cord-311035-s3tkbh9r 55 32 ) ) -RRB- cord-311035-s3tkbh9r 55 33 A a DT cord-311035-s3tkbh9r 55 34 library library NN cord-311035-s3tkbh9r 55 35 of of IN cord-311035-s3tkbh9r 55 36 ACE2 ACE2 NNP cord-311035-s3tkbh9r 55 37 variants variant NNS cord-311035-s3tkbh9r 55 38 was be VBD cord-311035-s3tkbh9r 55 39 expressed express VBN cord-311035-s3tkbh9r 55 40 in in IN cord-311035-s3tkbh9r 55 41 human human JJ cord-311035-s3tkbh9r 55 42 cells cell NNS cord-311035-s3tkbh9r 55 43 . . . cord-311035-s3tkbh9r 56 1 Full full JJ cord-311035-s3tkbh9r 56 2 - - HYPH cord-311035-s3tkbh9r 56 3 length length NN cord-311035-s3tkbh9r 56 4 ACE2 ACE2 NNP cord-311035-s3tkbh9r 56 5 ( ( -LRB- cord-311035-s3tkbh9r 56 6 tan tan NNP cord-311035-s3tkbh9r 56 7 ) ) -RRB- cord-311035-s3tkbh9r 56 8 was be VBD cord-311035-s3tkbh9r 56 9 tagged tag VBN cord-311035-s3tkbh9r 56 10 with with IN cord-311035-s3tkbh9r 56 11 a a DT cord-311035-s3tkbh9r 56 12 c c NNP cord-311035-s3tkbh9r 56 13 - - HYPH cord-311035-s3tkbh9r 56 14 myc myc NNP cord-311035-s3tkbh9r 56 15 epitope epitope NN cord-311035-s3tkbh9r 56 16 at at IN cord-311035-s3tkbh9r 56 17 its -PRON- PRP$ cord-311035-s3tkbh9r 56 18 extracellular extracellular JJ cord-311035-s3tkbh9r 56 19 N n CD cord-311035-s3tkbh9r 56 20 - - HYPH cord-311035-s3tkbh9r 56 21 terminus terminus NN cord-311035-s3tkbh9r 56 22 for for IN cord-311035-s3tkbh9r 56 23 detection detection NN cord-311035-s3tkbh9r 56 24 of of IN cord-311035-s3tkbh9r 56 25 surface surface NN cord-311035-s3tkbh9r 56 26 expression expression NN cord-311035-s3tkbh9r 56 27 with with IN cord-311035-s3tkbh9r 56 28 a a DT cord-311035-s3tkbh9r 56 29 fluorescent fluorescent JJ cord-311035-s3tkbh9r 56 30 antibody antibody NN cord-311035-s3tkbh9r 56 31 ( ( -LRB- cord-311035-s3tkbh9r 56 32 red red NNP cord-311035-s3tkbh9r 56 33 ) ) -RRB- cord-311035-s3tkbh9r 56 34 . . . cord-311035-s3tkbh9r 57 1 SARS SARS NNP cord-311035-s3tkbh9r 57 2 - - HYPH cord-311035-s3tkbh9r 57 3 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 57 4 RBD RBD NNP cord-311035-s3tkbh9r 58 1 ( ( -LRB- cord-311035-s3tkbh9r 58 2 pale pale JJ cord-311035-s3tkbh9r 58 3 green green JJ cord-311035-s3tkbh9r 58 4 ) ) -RRB- cord-311035-s3tkbh9r 58 5 genetically genetically RB cord-311035-s3tkbh9r 58 6 fused fuse VBN cord-311035-s3tkbh9r 58 7 with with IN cord-311035-s3tkbh9r 58 8 superfolder superfolder NN cord-311035-s3tkbh9r 58 9 green green JJ cord-311035-s3tkbh9r 58 10 fluorescent fluorescent NN cord-311035-s3tkbh9r 58 11 protein protein NN cord-311035-s3tkbh9r 58 12 ( ( -LRB- cord-311035-s3tkbh9r 58 13 sfGFP sfGFP NNP cord-311035-s3tkbh9r 58 14 ; ; : cord-311035-s3tkbh9r 58 15 dark dark JJ cord-311035-s3tkbh9r 58 16 green green NNP cord-311035-s3tkbh9r 58 17 ) ) -RRB- cord-311035-s3tkbh9r 58 18 was be VBD cord-311035-s3tkbh9r 58 19 incubated incubate VBN cord-311035-s3tkbh9r 58 20 with with IN cord-311035-s3tkbh9r 58 21 the the DT cord-311035-s3tkbh9r 58 22 cell cell NN cord-311035-s3tkbh9r 58 23 culture culture NN cord-311035-s3tkbh9r 58 24 . . . cord-311035-s3tkbh9r 59 1 FACS FACS NNP cord-311035-s3tkbh9r 59 2 was be VBD cord-311035-s3tkbh9r 59 3 used use VBN cord-311035-s3tkbh9r 59 4 to to TO cord-311035-s3tkbh9r 59 5 collect collect VB cord-311035-s3tkbh9r 59 6 fluorescent fluorescent NN cord-311035-s3tkbh9r 59 7 cells cell NNS cord-311035-s3tkbh9r 59 8 expressing express VBG cord-311035-s3tkbh9r 59 9 ACE2 ACE2 NNP cord-311035-s3tkbh9r 59 10 with with IN cord-311035-s3tkbh9r 59 11 bound bind VBN cord-311035-s3tkbh9r 59 12 RBD RBD NNP cord-311035-s3tkbh9r 59 13 - - HYPH cord-311035-s3tkbh9r 59 14 sfGFP sfGFP NNP cord-311035-s3tkbh9r 59 15 . . . cord-311035-s3tkbh9r 60 1 ( ( -LRB- cord-311035-s3tkbh9r 60 2 B b NN cord-311035-s3tkbh9r 60 3 ) ) -RRB- cord-311035-s3tkbh9r 61 1 The the DT cord-311035-s3tkbh9r 61 2 isolated isolated JJ cord-311035-s3tkbh9r 61 3 RBD RBD NNP cord-311035-s3tkbh9r 61 4 of of IN cord-311035-s3tkbh9r 61 5 SARS SARS NNP cord-311035-s3tkbh9r 61 6 - - HYPH cord-311035-s3tkbh9r 61 7 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 61 8 ( ( -LRB- cord-311035-s3tkbh9r 61 9 pale pale JJ cord-311035-s3tkbh9r 61 10 green green JJ cord-311035-s3tkbh9r 61 11 ) ) -RRB- cord-311035-s3tkbh9r 61 12 was be VBD cord-311035-s3tkbh9r 61 13 fused fuse VBN cord-311035-s3tkbh9r 61 14 at at IN cord-311035-s3tkbh9r 61 15 its -PRON- PRP$ cord-311035-s3tkbh9r 61 16 N n CD cord-311035-s3tkbh9r 61 17 - - HYPH cord-311035-s3tkbh9r 61 18 terminus terminus NN cord-311035-s3tkbh9r 61 19 to to IN cord-311035-s3tkbh9r 61 20 Aga2p Aga2p NNP cord-311035-s3tkbh9r 61 21 ( ( -LRB- cord-311035-s3tkbh9r 61 22 blue blue NNP cord-311035-s3tkbh9r 61 23 ) ) -RRB- cord-311035-s3tkbh9r 61 24 and and CC cord-311035-s3tkbh9r 61 25 at at IN cord-311035-s3tkbh9r 61 26 its -PRON- PRP$ cord-311035-s3tkbh9r 61 27 C c NN cord-311035-s3tkbh9r 61 28 - - HYPH cord-311035-s3tkbh9r 61 29 terminus terminus NN cord-311035-s3tkbh9r 61 30 to to IN cord-311035-s3tkbh9r 61 31 a a DT cord-311035-s3tkbh9r 61 32 c c NNP cord-311035-s3tkbh9r 61 33 - - HYPH cord-311035-s3tkbh9r 61 34 myc myc NNP cord-311035-s3tkbh9r 61 35 epitope epitope NN cord-311035-s3tkbh9r 61 36 tag tag NN cord-311035-s3tkbh9r 61 37 . . . cord-311035-s3tkbh9r 62 1 A a DT cord-311035-s3tkbh9r 62 2 saturation saturation NN cord-311035-s3tkbh9r 62 3 mutagenesis mutagenesis NN cord-311035-s3tkbh9r 62 4 library library NN cord-311035-s3tkbh9r 62 5 of of IN cord-311035-s3tkbh9r 62 6 the the DT cord-311035-s3tkbh9r 62 7 RBD RBD NNP cord-311035-s3tkbh9r 62 8 was be VBD cord-311035-s3tkbh9r 62 9 expressed express VBN cord-311035-s3tkbh9r 62 10 on on IN cord-311035-s3tkbh9r 62 11 the the DT cord-311035-s3tkbh9r 62 12 yeast yeast NN cord-311035-s3tkbh9r 62 13 surface surface NN cord-311035-s3tkbh9r 62 14 . . . cord-311035-s3tkbh9r 63 1 Following follow VBG cord-311035-s3tkbh9r 63 2 induction induction NN cord-311035-s3tkbh9r 63 3 of of IN cord-311035-s3tkbh9r 63 4 RBD RBD NNP cord-311035-s3tkbh9r 63 5 expression expression NN cord-311035-s3tkbh9r 63 6 , , , cord-311035-s3tkbh9r 63 7 the the DT cord-311035-s3tkbh9r 63 8 yeast yeast NN cord-311035-s3tkbh9r 63 9 were be VBD cord-311035-s3tkbh9r 63 10 incubated incubate VBN cord-311035-s3tkbh9r 63 11 with with IN cord-311035-s3tkbh9r 63 12 dimeric dimeric JJ cord-311035-s3tkbh9r 63 13 , , , cord-311035-s3tkbh9r 63 14 biotinylated biotinylated JJ cord-311035-s3tkbh9r 63 15 sACE2 sACE2 NNP cord-311035-s3tkbh9r 63 16 ( ( -LRB- cord-311035-s3tkbh9r 63 17 tan tan NNP cord-311035-s3tkbh9r 63 18 ) ) -RRB- cord-311035-s3tkbh9r 63 19 . . . cord-311035-s3tkbh9r 64 1 Bound Bound NNP cord-311035-s3tkbh9r 64 2 ACE2 ACE2 NNP cord-311035-s3tkbh9r 64 3 was be VBD cord-311035-s3tkbh9r 64 4 detected detect VBN cord-311035-s3tkbh9r 64 5 with with IN cord-311035-s3tkbh9r 64 6 fluorescent fluorescent JJ cord-311035-s3tkbh9r 64 7 streptavidin streptavidin NNS cord-311035-s3tkbh9r 64 8 ( ( -LRB- cord-311035-s3tkbh9r 64 9 purple purple NN cord-311035-s3tkbh9r 64 10 ) ) -RRB- cord-311035-s3tkbh9r 64 11 and and CC cord-311035-s3tkbh9r 64 12 surface surface NN cord-311035-s3tkbh9r 64 13 expressed express VBD cord-311035-s3tkbh9r 64 14 RBD RBD NNP cord-311035-s3tkbh9r 64 15 was be VBD cord-311035-s3tkbh9r 64 16 detected detect VBN cord-311035-s3tkbh9r 64 17 with with IN cord-311035-s3tkbh9r 64 18 a a DT cord-311035-s3tkbh9r 64 19 fluorescent fluorescent JJ cord-311035-s3tkbh9r 64 20 antibody antibody NN cord-311035-s3tkbh9r 64 21 ( ( -LRB- cord-311035-s3tkbh9r 64 22 red red NNP cord-311035-s3tkbh9r 64 23 ) ) -RRB- cord-311035-s3tkbh9r 64 24 . . . cord-311035-s3tkbh9r 65 1 • • NNP cord-311035-s3tkbh9r 66 1 In in IN cord-311035-s3tkbh9r 66 2 deep deep JJ cord-311035-s3tkbh9r 66 3 mutagenesis mutagenesis NN cord-311035-s3tkbh9r 66 4 , , , cord-311035-s3tkbh9r 66 5 the the DT cord-311035-s3tkbh9r 66 6 relative relative JJ cord-311035-s3tkbh9r 66 7 phenotypes phenotype NNS cord-311035-s3tkbh9r 66 8 of of IN cord-311035-s3tkbh9r 66 9 thousands thousand NNS cord-311035-s3tkbh9r 66 10 of of IN cord-311035-s3tkbh9r 66 11 mutations mutation NNS cord-311035-s3tkbh9r 66 12 in in IN cord-311035-s3tkbh9r 66 13 a a DT cord-311035-s3tkbh9r 66 14 protein protein NN cord-311035-s3tkbh9r 66 15 sequence sequence NN cord-311035-s3tkbh9r 66 16 are be VBP cord-311035-s3tkbh9r 66 17 determined determine VBN cord-311035-s3tkbh9r 66 18 in in IN cord-311035-s3tkbh9r 66 19 a a DT cord-311035-s3tkbh9r 66 20 single single JJ cord-311035-s3tkbh9r 66 21 experiment experiment NN cord-311035-s3tkbh9r 66 22 . . . cord-311035-s3tkbh9r 67 1 • • NNP cord-311035-s3tkbh9r 68 1 The the DT cord-311035-s3tkbh9r 68 2 experimental experimental JJ cord-311035-s3tkbh9r 68 3 mutational mutational JJ cord-311035-s3tkbh9r 68 4 landscape landscape NN cord-311035-s3tkbh9r 68 5 of of IN cord-311035-s3tkbh9r 68 6 ACE2 ACE2 NNP cord-311035-s3tkbh9r 68 7 for for IN cord-311035-s3tkbh9r 68 8 binding bind VBG cord-311035-s3tkbh9r 68 9 the the DT cord-311035-s3tkbh9r 68 10 RBD RBD NNP cord-311035-s3tkbh9r 68 11 of of IN cord-311035-s3tkbh9r 68 12 SARS SARS NNP cord-311035-s3tkbh9r 68 13 - - HYPH cord-311035-s3tkbh9r 68 14 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 68 15 provides provide VBZ cord-311035-s3tkbh9r 68 16 a a DT cord-311035-s3tkbh9r 68 17 blueprint blueprint NN cord-311035-s3tkbh9r 68 18 for for IN cord-311035-s3tkbh9r 68 19 engineering engineer VBG cord-311035-s3tkbh9r 68 20 high high JJ cord-311035-s3tkbh9r 68 21 affinity affinity NN cord-311035-s3tkbh9r 68 22 decoy decoy NN cord-311035-s3tkbh9r 68 23 receptors receptor NNS cord-311035-s3tkbh9r 68 24 . . . cord-311035-s3tkbh9r 69 1 • • NNP cord-311035-s3tkbh9r 70 1 A a DT cord-311035-s3tkbh9r 70 2 deep deep JJ cord-311035-s3tkbh9r 70 3 mutational mutational JJ cord-311035-s3tkbh9r 70 4 scan scan NN cord-311035-s3tkbh9r 70 5 of of IN cord-311035-s3tkbh9r 70 6 the the DT cord-311035-s3tkbh9r 70 7 SARS SARS NNP cord-311035-s3tkbh9r 70 8 - - HYPH cord-311035-s3tkbh9r 70 9 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 70 10 RBD RBD NNP cord-311035-s3tkbh9r 70 11 reveals reveal VBZ cord-311035-s3tkbh9r 70 12 considerable considerable JJ cord-311035-s3tkbh9r 70 13 opportunity opportunity NN cord-311035-s3tkbh9r 70 14 for for IN cord-311035-s3tkbh9r 70 15 genetic genetic JJ cord-311035-s3tkbh9r 70 16 drift drift NN cord-311035-s3tkbh9r 70 17 without without IN cord-311035-s3tkbh9r 70 18 loss loss NN cord-311035-s3tkbh9r 70 19 of of IN cord-311035-s3tkbh9r 70 20 receptor receptor NN cord-311035-s3tkbh9r 70 21 affinity affinity NN cord-311035-s3tkbh9r 70 22 . . . cord-311035-s3tkbh9r 71 1 • • NNP cord-311035-s3tkbh9r 72 1 Different different JJ cord-311035-s3tkbh9r 72 2 expression expression NN cord-311035-s3tkbh9r 72 3 systems system NNS cord-311035-s3tkbh9r 72 4 for for IN cord-311035-s3tkbh9r 72 5 selecting select VBG cord-311035-s3tkbh9r 72 6 ACE2 ACE2 NNP cord-311035-s3tkbh9r 72 7 or or CC cord-311035-s3tkbh9r 72 8 spike spike NN cord-311035-s3tkbh9r 72 9 variants variant NNS cord-311035-s3tkbh9r 72 10 have have VBP cord-311035-s3tkbh9r 72 11 inherent inherent JJ cord-311035-s3tkbh9r 72 12 advantages advantage NNS cord-311035-s3tkbh9r 72 13 and and CC cord-311035-s3tkbh9r 72 14 disadvantages disadvantage NNS cord-311035-s3tkbh9r 72 15 . . . cord-311035-s3tkbh9r 73 1 • • NNP cord-311035-s3tkbh9r 74 1 There there EX cord-311035-s3tkbh9r 74 2 are be VBP cord-311035-s3tkbh9r 74 3 opportunities opportunity NNS cord-311035-s3tkbh9r 74 4 for for IN cord-311035-s3tkbh9r 74 5 deep deep JJ cord-311035-s3tkbh9r 74 6 mutagenesis mutagenesis NN cord-311035-s3tkbh9r 74 7 to to TO cord-311035-s3tkbh9r 74 8 provide provide VB cord-311035-s3tkbh9r 74 9 biochemical biochemical JJ cord-311035-s3tkbh9r 74 10 insights insight NNS cord-311035-s3tkbh9r 74 11 on on IN cord-311035-s3tkbh9r 74 12 other other JJ cord-311035-s3tkbh9r 74 13 SARS SARS NNP cord-311035-s3tkbh9r 74 14 - - HYPH cord-311035-s3tkbh9r 74 15 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 74 16 proteins protein NNS cord-311035-s3tkbh9r 74 17 . . . cord-311035-s3tkbh9r 75 1 culture culture NN cord-311035-s3tkbh9r 75 2 do do VBP cord-311035-s3tkbh9r 75 3 not not RB cord-311035-s3tkbh9r 75 4 express express VB cord-311035-s3tkbh9r 75 5 ACE2 ACE2 NNP cord-311035-s3tkbh9r 75 6 and and CC cord-311035-s3tkbh9r 75 7 FACS FACS NNP cord-311035-s3tkbh9r 75 8 time time NN cord-311035-s3tkbh9r 75 9 is be VBZ cord-311035-s3tkbh9r 75 10 wasted waste VBN cord-311035-s3tkbh9r 75 11 on on IN cord-311035-s3tkbh9r 75 12 sorting sort VBG cord-311035-s3tkbh9r 75 13 a a DT cord-311035-s3tkbh9r 75 14 large large JJ cord-311035-s3tkbh9r 75 15 number number NN cord-311035-s3tkbh9r 75 16 of of IN cord-311035-s3tkbh9r 75 17 negative negative JJ cord-311035-s3tkbh9r 75 18 cells cell NNS cord-311035-s3tkbh9r 75 19 . . . cord-311035-s3tkbh9r 76 1 This this DT cord-311035-s3tkbh9r 76 2 has have VBZ cord-311035-s3tkbh9r 76 3 important important JJ cord-311035-s3tkbh9r 76 4 consequences consequence NNS cord-311035-s3tkbh9r 76 5 on on IN cord-311035-s3tkbh9r 76 6 the the DT cord-311035-s3tkbh9r 76 7 data datum NNS cord-311035-s3tkbh9r 76 8 , , , cord-311035-s3tkbh9r 76 9 as as IN cord-311035-s3tkbh9r 76 10 time time NN cord-311035-s3tkbh9r 76 11 spent spend VBD cord-311035-s3tkbh9r 76 12 sampling sampling NN cord-311035-s3tkbh9r 76 13 negative negative JJ cord-311035-s3tkbh9r 76 14 cells cell NNS cord-311035-s3tkbh9r 76 15 is be VBZ cord-311035-s3tkbh9r 76 16 time time NN cord-311035-s3tkbh9r 76 17 not not RB cord-311035-s3tkbh9r 76 18 spent spend VBD cord-311035-s3tkbh9r 76 19 sampling sampling NN cord-311035-s3tkbh9r 76 20 cells cell NNS cord-311035-s3tkbh9r 76 21 expressing express VBG cord-311035-s3tkbh9r 76 22 the the DT cord-311035-s3tkbh9r 76 23 protein protein NN cord-311035-s3tkbh9r 76 24 under under IN cord-311035-s3tkbh9r 76 25 investigation investigation NN cord-311035-s3tkbh9r 76 26 , , , cord-311035-s3tkbh9r 76 27 and and CC cord-311035-s3tkbh9r 76 28 consequently consequently RB cord-311035-s3tkbh9r 76 29 variants variant VBZ cord-311035-s3tkbh9r 76 30 in in IN cord-311035-s3tkbh9r 76 31 the the DT cord-311035-s3tkbh9r 76 32 library library NN cord-311035-s3tkbh9r 76 33 may may MD cord-311035-s3tkbh9r 76 34 be be VB cord-311035-s3tkbh9r 76 35 under under RB cord-311035-s3tkbh9r 76 36 - - HYPH cord-311035-s3tkbh9r 76 37 sampled sample VBN cord-311035-s3tkbh9r 76 38 giving give VBG cord-311035-s3tkbh9r 76 39 poor poor JJ cord-311035-s3tkbh9r 76 40 data datum NNS cord-311035-s3tkbh9r 76 41 accuracy accuracy NN cord-311035-s3tkbh9r 76 42 . . . cord-311035-s3tkbh9r 77 1 Undersampling Undersampling NNP cord-311035-s3tkbh9r 77 2 becomes become VBZ cord-311035-s3tkbh9r 77 3 exceptionally exceptionally RB cord-311035-s3tkbh9r 77 4 concerning concern VBG cord-311035-s3tkbh9r 77 5 as as IN cord-311035-s3tkbh9r 77 6 the the DT cord-311035-s3tkbh9r 77 7 library library NN cord-311035-s3tkbh9r 77 8 size size NN cord-311035-s3tkbh9r 77 9 increases increase NNS cord-311035-s3tkbh9r 77 10 , , , cord-311035-s3tkbh9r 77 11 and and CC cord-311035-s3tkbh9r 77 12 for for IN cord-311035-s3tkbh9r 77 13 this this DT cord-311035-s3tkbh9r 77 14 reason reason NN cord-311035-s3tkbh9r 77 15 the the DT cord-311035-s3tkbh9r 77 16 library library NN cord-311035-s3tkbh9r 77 17 was be VBD cord-311035-s3tkbh9r 77 18 limited limit VBN cord-311035-s3tkbh9r 77 19 to to IN cord-311035-s3tkbh9r 77 20 single single JJ cord-311035-s3tkbh9r 77 21 amino amino NN cord-311035-s3tkbh9r 77 22 acid acid NN cord-311035-s3tkbh9r 77 23 substitutions substitution NNS cord-311035-s3tkbh9r 77 24 at at IN cord-311035-s3tkbh9r 77 25 just just RB cord-311035-s3tkbh9r 77 26 117 117 CD cord-311035-s3tkbh9r 77 27 positions position NNS cord-311035-s3tkbh9r 77 28 in in IN cord-311035-s3tkbh9r 77 29 ACE2 ACE2 NNP cord-311035-s3tkbh9r 77 30 . . . cord-311035-s3tkbh9r 78 1 Following follow VBG cord-311035-s3tkbh9r 78 2 FACS FACS NNP cord-311035-s3tkbh9r 78 3 selection selection NN cord-311035-s3tkbh9r 78 4 of of IN cord-311035-s3tkbh9r 78 5 the the DT cord-311035-s3tkbh9r 78 6 human human JJ cord-311035-s3tkbh9r 78 7 culture culture NN cord-311035-s3tkbh9r 78 8 to to TO cord-311035-s3tkbh9r 78 9 enrich enrich VB cord-311035-s3tkbh9r 78 10 a a DT cord-311035-s3tkbh9r 78 11 cell cell NN cord-311035-s3tkbh9r 78 12 population population NN cord-311035-s3tkbh9r 78 13 with with IN cord-311035-s3tkbh9r 78 14 high high JJ cord-311035-s3tkbh9r 78 15 binding binding NN cord-311035-s3tkbh9r 78 16 activity activity NN cord-311035-s3tkbh9r 78 17 for for IN cord-311035-s3tkbh9r 78 18 SARS SARS NNP cord-311035-s3tkbh9r 78 19 - - HYPH cord-311035-s3tkbh9r 78 20 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 78 21 protein protein NN cord-311035-s3tkbh9r 78 22 S S NNP cord-311035-s3tkbh9r 78 23 , , , cord-311035-s3tkbh9r 78 24 RNA RNA NNP cord-311035-s3tkbh9r 78 25 transcripts transcript NNS cord-311035-s3tkbh9r 78 26 were be VBD cord-311035-s3tkbh9r 78 27 isolated isolate VBN cord-311035-s3tkbh9r 78 28 and and CC cord-311035-s3tkbh9r 78 29 Illumina Illumina NNP cord-311035-s3tkbh9r 78 30 sequenced sequence VBN cord-311035-s3tkbh9r 78 31 . . . cord-311035-s3tkbh9r 79 1 An an DT cord-311035-s3tkbh9r 79 2 enrichment enrichment NN cord-311035-s3tkbh9r 79 3 ratio ratio NN cord-311035-s3tkbh9r 79 4 is be VBZ cord-311035-s3tkbh9r 79 5 calculated calculate VBN cord-311035-s3tkbh9r 79 6 for for IN cord-311035-s3tkbh9r 79 7 each each DT cord-311035-s3tkbh9r 79 8 mutation mutation NN cord-311035-s3tkbh9r 79 9 by by IN cord-311035-s3tkbh9r 79 10 dividing divide VBG cord-311035-s3tkbh9r 79 11 its -PRON- PRP$ cord-311035-s3tkbh9r 79 12 frequency frequency NN cord-311035-s3tkbh9r 79 13 in in IN cord-311035-s3tkbh9r 79 14 the the DT cord-311035-s3tkbh9r 79 15 sorted sorted JJ cord-311035-s3tkbh9r 79 16 cell cell NN cord-311035-s3tkbh9r 79 17 transcripts transcript NNS cord-311035-s3tkbh9r 79 18 by by IN cord-311035-s3tkbh9r 79 19 its -PRON- PRP$ cord-311035-s3tkbh9r 79 20 frequency frequency NN cord-311035-s3tkbh9r 79 21 in in IN cord-311035-s3tkbh9r 79 22 the the DT cord-311035-s3tkbh9r 79 23 naive naive JJ cord-311035-s3tkbh9r 79 24 plasmid plasmid NN cord-311035-s3tkbh9r 79 25 library library NN cord-311035-s3tkbh9r 79 26 [ [ -LRB- cord-311035-s3tkbh9r 79 27 51 51 CD cord-311035-s3tkbh9r 79 28 ] ] -RRB- cord-311035-s3tkbh9r 79 29 . . . cord-311035-s3tkbh9r 80 1 Illumina Illumina NNP cord-311035-s3tkbh9r 80 2 sequencing sequencing NN cord-311035-s3tkbh9r 80 3 did do VBD cord-311035-s3tkbh9r 80 4 not not RB cord-311035-s3tkbh9r 80 5 cover cover VB cord-311035-s3tkbh9r 80 6 the the DT cord-311035-s3tkbh9r 80 7 full full JJ cord-311035-s3tkbh9r 80 8 length length NN cord-311035-s3tkbh9r 80 9 of of IN cord-311035-s3tkbh9r 80 10 ACE2 ACE2 NNP cord-311035-s3tkbh9r 80 11 and and CC cord-311035-s3tkbh9r 80 12 instead instead RB cord-311035-s3tkbh9r 80 13 the the DT cord-311035-s3tkbh9r 80 14 cDNA cdna NN cord-311035-s3tkbh9r 80 15 was be VBD cord-311035-s3tkbh9r 80 16 sequenced sequence VBN cord-311035-s3tkbh9r 80 17 as as IN cord-311035-s3tkbh9r 80 18 a a DT cord-311035-s3tkbh9r 80 19 series series NN cord-311035-s3tkbh9r 80 20 of of IN cord-311035-s3tkbh9r 80 21 fragments fragment NNS cord-311035-s3tkbh9r 80 22 that that WDT cord-311035-s3tkbh9r 80 23 together together RB cord-311035-s3tkbh9r 80 24 provided provide VBD cord-311035-s3tkbh9r 80 25 full full JJ cord-311035-s3tkbh9r 80 26 coverage coverage NN cord-311035-s3tkbh9r 80 27 of of IN cord-311035-s3tkbh9r 80 28 the the DT cord-311035-s3tkbh9r 80 29 diversified diversified JJ cord-311035-s3tkbh9r 80 30 regions region NNS cord-311035-s3tkbh9r 80 31 . . . cord-311035-s3tkbh9r 81 1 One one PRP cord-311035-s3tkbh9r 81 2 assumes assume VBZ cord-311035-s3tkbh9r 81 3 during during IN cord-311035-s3tkbh9r 81 4 analysis analysis NN cord-311035-s3tkbh9r 81 5 that that IN cord-311035-s3tkbh9r 81 6 there there EX cord-311035-s3tkbh9r 81 7 are be VBP cord-311035-s3tkbh9r 81 8 no no DT cord-311035-s3tkbh9r 81 9 additional additional JJ cord-311035-s3tkbh9r 81 10 mutations mutation NNS cord-311035-s3tkbh9r 81 11 outside outside IN cord-311035-s3tkbh9r 81 12 a a DT cord-311035-s3tkbh9r 81 13 sequenced sequence VBN cord-311035-s3tkbh9r 81 14 fragment fragment NN cord-311035-s3tkbh9r 81 15 , , , cord-311035-s3tkbh9r 81 16 a a DT cord-311035-s3tkbh9r 81 17 reasonable reasonable JJ cord-311035-s3tkbh9r 81 18 assumption assumption NN cord-311035-s3tkbh9r 81 19 when when WRB cord-311035-s3tkbh9r 81 20 a a DT cord-311035-s3tkbh9r 81 21 mutation mutation NN cord-311035-s3tkbh9r 81 22 is be VBZ cord-311035-s3tkbh9r 81 23 found find VBN cord-311035-s3tkbh9r 81 24 because because IN cord-311035-s3tkbh9r 81 25 the the DT cord-311035-s3tkbh9r 81 26 library library NN cord-311035-s3tkbh9r 81 27 was be VBD cord-311035-s3tkbh9r 81 28 constructed construct VBN cord-311035-s3tkbh9r 81 29 to to TO cord-311035-s3tkbh9r 81 30 have have VB cord-311035-s3tkbh9r 81 31 only only RB cord-311035-s3tkbh9r 81 32 one one CD cord-311035-s3tkbh9r 81 33 amino amino NN cord-311035-s3tkbh9r 81 34 acid acid NN cord-311035-s3tkbh9r 81 35 substitution substitution NN cord-311035-s3tkbh9r 81 36 per per IN cord-311035-s3tkbh9r 81 37 plasmid plasmid NN cord-311035-s3tkbh9r 81 38 . . . cord-311035-s3tkbh9r 82 1 However however RB cord-311035-s3tkbh9r 82 2 , , , cord-311035-s3tkbh9r 82 3 the the DT cord-311035-s3tkbh9r 82 4 assumption assumption NN cord-311035-s3tkbh9r 82 5 breaks break VBZ cord-311035-s3tkbh9r 82 6 down down RP cord-311035-s3tkbh9r 82 7 when when WRB cord-311035-s3tkbh9r 82 8 no no DT cord-311035-s3tkbh9r 82 9 mutations mutation NNS cord-311035-s3tkbh9r 82 10 are be VBP cord-311035-s3tkbh9r 82 11 observed observe VBN cord-311035-s3tkbh9r 82 12 in in IN cord-311035-s3tkbh9r 82 13 the the DT cord-311035-s3tkbh9r 82 14 sequenced sequence VBN cord-311035-s3tkbh9r 82 15 fragment fragment NN cord-311035-s3tkbh9r 82 16 , , , cord-311035-s3tkbh9r 82 17 as as IN cord-311035-s3tkbh9r 82 18 one one PRP cord-311035-s3tkbh9r 82 19 can can MD cord-311035-s3tkbh9r 82 20 not not RB cord-311035-s3tkbh9r 82 21 know know VB cord-311035-s3tkbh9r 82 22 whether whether IN cord-311035-s3tkbh9r 82 23 there there EX cord-311035-s3tkbh9r 82 24 was be VBD cord-311035-s3tkbh9r 82 25 a a DT cord-311035-s3tkbh9r 82 26 mutation mutation NN cord-311035-s3tkbh9r 82 27 elsewhere elsewhere RB cord-311035-s3tkbh9r 82 28 outside outside IN cord-311035-s3tkbh9r 82 29 the the DT cord-311035-s3tkbh9r 82 30 sequenced sequence VBN cord-311035-s3tkbh9r 82 31 region region NN cord-311035-s3tkbh9r 82 32 . . . cord-311035-s3tkbh9r 83 1 As as IN cord-311035-s3tkbh9r 83 2 a a DT cord-311035-s3tkbh9r 83 3 consequence consequence NN cord-311035-s3tkbh9r 83 4 , , , cord-311035-s3tkbh9r 83 5 the the DT cord-311035-s3tkbh9r 83 6 wild wild JJ cord-311035-s3tkbh9r 83 7 type type NN cord-311035-s3tkbh9r 83 8 sequence sequence NN cord-311035-s3tkbh9r 83 9 is be VBZ cord-311035-s3tkbh9r 83 10 not not RB cord-311035-s3tkbh9r 83 11 directly directly RB cord-311035-s3tkbh9r 83 12 observed observe VBN cord-311035-s3tkbh9r 83 13 and and CC cord-311035-s3tkbh9r 83 14 is be VBZ cord-311035-s3tkbh9r 83 15 instead instead RB cord-311035-s3tkbh9r 83 16 only only RB cord-311035-s3tkbh9r 83 17 estimated estimate VBN cord-311035-s3tkbh9r 83 18 . . . cord-311035-s3tkbh9r 84 1 There there EX cord-311035-s3tkbh9r 84 2 are be VBP cord-311035-s3tkbh9r 84 3 strategies strategy NNS cord-311035-s3tkbh9r 84 4 using use VBG cord-311035-s3tkbh9r 84 5 the the DT cord-311035-s3tkbh9r 84 6 introduction introduction NN cord-311035-s3tkbh9r 84 7 and and CC cord-311035-s3tkbh9r 84 8 analysis analysis NN cord-311035-s3tkbh9r 84 9 of of IN cord-311035-s3tkbh9r 84 10 silent silent JJ cord-311035-s3tkbh9r 84 11 mutations mutation NNS cord-311035-s3tkbh9r 84 12 that that WDT cord-311035-s3tkbh9r 84 13 can can MD cord-311035-s3tkbh9r 84 14 resolve resolve VB cord-311035-s3tkbh9r 84 15 this this DT cord-311035-s3tkbh9r 84 16 issue issue NN cord-311035-s3tkbh9r 84 17 [ [ -LRB- cord-311035-s3tkbh9r 84 18 52 52 CD cord-311035-s3tkbh9r 84 19 ] ] -RRB- cord-311035-s3tkbh9r 84 20 . . . cord-311035-s3tkbh9r 85 1 Overall overall RB cord-311035-s3tkbh9r 85 2 , , , cord-311035-s3tkbh9r 85 3 there there EX cord-311035-s3tkbh9r 85 4 was be VBD cord-311035-s3tkbh9r 85 5 close close JJ cord-311035-s3tkbh9r 85 6 agreement agreement NN cord-311035-s3tkbh9r 85 7 between between IN cord-311035-s3tkbh9r 85 8 the the DT cord-311035-s3tkbh9r 85 9 mutation mutation NN cord-311035-s3tkbh9r 85 10 enrichment enrichment NN cord-311035-s3tkbh9r 85 11 ratios ratio NNS cord-311035-s3tkbh9r 85 12 from from IN cord-311035-s3tkbh9r 85 13 two two CD cord-311035-s3tkbh9r 85 14 independent independent JJ cord-311035-s3tkbh9r 85 15 replicates replicate NNS cord-311035-s3tkbh9r 85 16 of of IN cord-311035-s3tkbh9r 85 17 the the DT cord-311035-s3tkbh9r 85 18 FACS FACS NNP cord-311035-s3tkbh9r 85 19 experiments experiment NNS cord-311035-s3tkbh9r 85 20 , , , cord-311035-s3tkbh9r 85 21 indicating indicate VBG cord-311035-s3tkbh9r 85 22 that that IN cord-311035-s3tkbh9r 85 23 the the DT cord-311035-s3tkbh9r 85 24 ACE2 ACE2 NNP cord-311035-s3tkbh9r 85 25 library library NN cord-311035-s3tkbh9r 85 26 was be VBD cord-311035-s3tkbh9r 85 27 well well RB cord-311035-s3tkbh9r 85 28 sampled sample VBN cord-311035-s3tkbh9r 85 29 and and CC cord-311035-s3tkbh9r 85 30 there there EX cord-311035-s3tkbh9r 85 31 was be VBD cord-311035-s3tkbh9r 85 32 high high JJ cord-311035-s3tkbh9r 85 33 confidence confidence NN cord-311035-s3tkbh9r 85 34 in in IN cord-311035-s3tkbh9r 85 35 the the DT cord-311035-s3tkbh9r 85 36 data datum NNS cord-311035-s3tkbh9r 85 37 [ [ -LRB- cord-311035-s3tkbh9r 85 38 15 15 CD cord-311035-s3tkbh9r 85 39 ] ] -RRB- cord-311035-s3tkbh9r 85 40 . . . cord-311035-s3tkbh9r 86 1 The the DT cord-311035-s3tkbh9r 86 2 enrichment enrichment NN cord-311035-s3tkbh9r 86 3 ratios ratio NNS cord-311035-s3tkbh9r 86 4 calculated calculate VBN cord-311035-s3tkbh9r 86 5 for for IN cord-311035-s3tkbh9r 86 6 each each DT cord-311035-s3tkbh9r 86 7 variant variant NN cord-311035-s3tkbh9r 86 8 in in IN cord-311035-s3tkbh9r 86 9 the the DT cord-311035-s3tkbh9r 86 10 sorted sorted JJ cord-311035-s3tkbh9r 86 11 ACE2 ACE2 NNP cord-311035-s3tkbh9r 86 12 library library NN cord-311035-s3tkbh9r 86 13 provide provide VBP cord-311035-s3tkbh9r 86 14 a a DT cord-311035-s3tkbh9r 86 15 mutational mutational JJ cord-311035-s3tkbh9r 86 16 landscape landscape NN cord-311035-s3tkbh9r 86 17 that that WDT cord-311035-s3tkbh9r 86 18 defines define VBZ cord-311035-s3tkbh9r 86 19 the the DT cord-311035-s3tkbh9r 86 20 relative relative JJ cord-311035-s3tkbh9r 86 21 phenotypes phenotype NNS cord-311035-s3tkbh9r 86 22 of of IN cord-311035-s3tkbh9r 86 23 thousands thousand NNS cord-311035-s3tkbh9r 86 24 of of IN cord-311035-s3tkbh9r 86 25 ACE2 ACE2 NNP cord-311035-s3tkbh9r 86 26 mutations mutation NNS cord-311035-s3tkbh9r 86 27 for for IN cord-311035-s3tkbh9r 86 28 binding bind VBG cord-311035-s3tkbh9r 86 29 to to IN cord-311035-s3tkbh9r 86 30 SARS SARS NNP cord-311035-s3tkbh9r 86 31 - - HYPH cord-311035-s3tkbh9r 86 32 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 86 33 S S NNP cord-311035-s3tkbh9r 86 34 [ [ -LRB- cord-311035-s3tkbh9r 86 35 15 15 CD cord-311035-s3tkbh9r 86 36 ] ] -RRB- cord-311035-s3tkbh9r 86 37 . . . cord-311035-s3tkbh9r 87 1 The the DT cord-311035-s3tkbh9r 87 2 data datum NNS cord-311035-s3tkbh9r 87 3 in in IN cord-311035-s3tkbh9r 87 4 this this DT cord-311035-s3tkbh9r 87 5 experiment experiment NN cord-311035-s3tkbh9r 87 6 are be VBP cord-311035-s3tkbh9r 87 7 qualitative qualitative JJ cord-311035-s3tkbh9r 87 8 and and CC cord-311035-s3tkbh9r 87 9 it -PRON- PRP cord-311035-s3tkbh9r 87 10 is be VBZ cord-311035-s3tkbh9r 87 11 unclear unclear JJ cord-311035-s3tkbh9r 87 12 how how WRB cord-311035-s3tkbh9r 87 13 a a DT cord-311035-s3tkbh9r 87 14 log log NN cord-311035-s3tkbh9r 87 15 2 2 CD cord-311035-s3tkbh9r 87 16 enrichment enrichment NN cord-311035-s3tkbh9r 87 17 ratio ratio NN cord-311035-s3tkbh9r 87 18 of of IN cord-311035-s3tkbh9r 87 19 , , , cord-311035-s3tkbh9r 87 20 say say UH cord-311035-s3tkbh9r 87 21 , , , cord-311035-s3tkbh9r 87 22 −2 −2 NNP cord-311035-s3tkbh9r 87 23 or or CC cord-311035-s3tkbh9r 87 24 +3 +3 NNP cord-311035-s3tkbh9r 87 25 translates translate VBZ cord-311035-s3tkbh9r 87 26 to to IN cord-311035-s3tkbh9r 87 27 an an DT cord-311035-s3tkbh9r 87 28 exact exact JJ cord-311035-s3tkbh9r 87 29 change change NN cord-311035-s3tkbh9r 87 30 in in IN cord-311035-s3tkbh9r 87 31 a a DT cord-311035-s3tkbh9r 87 32 biophysical biophysical JJ cord-311035-s3tkbh9r 87 33 parameter parameter NN cord-311035-s3tkbh9r 87 34 such such JJ cord-311035-s3tkbh9r 87 35 as as IN cord-311035-s3tkbh9r 87 36 K K NNP cord-311035-s3tkbh9r 87 37 D D NNP cord-311035-s3tkbh9r 87 38 . . . cord-311035-s3tkbh9r 88 1 Furthermore furthermore RB cord-311035-s3tkbh9r 88 2 , , , cord-311035-s3tkbh9r 88 3 mutations mutation NNS cord-311035-s3tkbh9r 88 4 can can MD cord-311035-s3tkbh9r 88 5 impact impact VB cord-311035-s3tkbh9r 88 6 not not RB cord-311035-s3tkbh9r 88 7 only only RB cord-311035-s3tkbh9r 88 8 binding bind VBG cord-311035-s3tkbh9r 88 9 affinity affinity NN cord-311035-s3tkbh9r 88 10 for for IN cord-311035-s3tkbh9r 88 11 the the DT cord-311035-s3tkbh9r 88 12 RBD RBD NNP cord-311035-s3tkbh9r 88 13 of of IN cord-311035-s3tkbh9r 88 14 S S NNP cord-311035-s3tkbh9r 88 15 but but CC cord-311035-s3tkbh9r 88 16 also also RB cord-311035-s3tkbh9r 88 17 ACE2 ACE2 NNP cord-311035-s3tkbh9r 88 18 surface surface NN cord-311035-s3tkbh9r 88 19 expression expression NN cord-311035-s3tkbh9r 88 20 . . . cord-311035-s3tkbh9r 89 1 To to TO cord-311035-s3tkbh9r 89 2 filter filter VB cord-311035-s3tkbh9r 89 3 out out RP cord-311035-s3tkbh9r 89 4 the the DT cord-311035-s3tkbh9r 89 5 contribution contribution NN cord-311035-s3tkbh9r 89 6 of of IN cord-311035-s3tkbh9r 89 7 mutations mutation NNS cord-311035-s3tkbh9r 89 8 to to IN cord-311035-s3tkbh9r 89 9 expression expression NN cord-311035-s3tkbh9r 89 10 , , , cord-311035-s3tkbh9r 89 11 two two CD cord-311035-s3tkbh9r 89 12 populations population NNS cord-311035-s3tkbh9r 89 13 of of IN cord-311035-s3tkbh9r 89 14 cells cell NNS cord-311035-s3tkbh9r 89 15 were be VBD cord-311035-s3tkbh9r 89 16 collected collect VBN cord-311035-s3tkbh9r 89 17 by by IN cord-311035-s3tkbh9r 89 18 FACS FACS NNP cord-311035-s3tkbh9r 89 19 . . . cord-311035-s3tkbh9r 90 1 In in IN cord-311035-s3tkbh9r 90 2 addition addition NN cord-311035-s3tkbh9r 90 3 to to IN cord-311035-s3tkbh9r 90 4 collecting collect VBG cord-311035-s3tkbh9r 90 5 cells cell NNS cord-311035-s3tkbh9r 90 6 that that WDT cord-311035-s3tkbh9r 90 7 express express VBP cord-311035-s3tkbh9r 90 8 ACE2 ACE2 NNP cord-311035-s3tkbh9r 90 9 and and CC cord-311035-s3tkbh9r 90 10 tightly tightly RB cord-311035-s3tkbh9r 90 11 bind bind VB cord-311035-s3tkbh9r 90 12 RBD RBD NNP cord-311035-s3tkbh9r 90 13 , , , cord-311035-s3tkbh9r 90 14 cells cell NNS cord-311035-s3tkbh9r 90 15 were be VBD cord-311035-s3tkbh9r 90 16 simultaneously simultaneously RB cord-311035-s3tkbh9r 90 17 collected collect VBN cord-311035-s3tkbh9r 90 18 in in IN cord-311035-s3tkbh9r 90 19 the the DT cord-311035-s3tkbh9r 90 20 same same JJ cord-311035-s3tkbh9r 90 21 experiment experiment NN cord-311035-s3tkbh9r 90 22 that that WDT cord-311035-s3tkbh9r 90 23 express express VBP cord-311035-s3tkbh9r 90 24 ACE2 ACE2 NNP cord-311035-s3tkbh9r 90 25 but but CC cord-311035-s3tkbh9r 90 26 have have VBP cord-311035-s3tkbh9r 90 27 weak weak JJ cord-311035-s3tkbh9r 90 28 RBD RBD NNP cord-311035-s3tkbh9r 90 29 binding binding NN cord-311035-s3tkbh9r 90 30 . . . cord-311035-s3tkbh9r 91 1 ACE2 ACE2 NNP cord-311035-s3tkbh9r 91 2 mutants mutant NNS cord-311035-s3tkbh9r 91 3 that that WDT cord-311035-s3tkbh9r 91 4 were be VBD cord-311035-s3tkbh9r 91 5 not not RB cord-311035-s3tkbh9r 91 6 expressed express VBN cord-311035-s3tkbh9r 91 7 at at IN cord-311035-s3tkbh9r 91 8 the the DT cord-311035-s3tkbh9r 91 9 cell cell NN cord-311035-s3tkbh9r 91 10 surface surface NN cord-311035-s3tkbh9r 91 11 would would MD cord-311035-s3tkbh9r 91 12 be be VB cord-311035-s3tkbh9r 91 13 depleted deplete VBN cord-311035-s3tkbh9r 91 14 from from IN cord-311035-s3tkbh9r 91 15 both both DT cord-311035-s3tkbh9r 91 16 sorted sort VBN cord-311035-s3tkbh9r 91 17 populations population NNS cord-311035-s3tkbh9r 91 18 , , , cord-311035-s3tkbh9r 91 19 which which WDT cord-311035-s3tkbh9r 91 20 was be VBD cord-311035-s3tkbh9r 91 21 apparent apparent JJ cord-311035-s3tkbh9r 91 22 from from IN cord-311035-s3tkbh9r 91 23 tracking track VBG cord-311035-s3tkbh9r 91 24 the the DT cord-311035-s3tkbh9r 91 25 depletion depletion NN cord-311035-s3tkbh9r 91 26 of of IN cord-311035-s3tkbh9r 91 27 nonsense nonsense NN cord-311035-s3tkbh9r 91 28 mutations mutation NNS cord-311035-s3tkbh9r 91 29 . . . cord-311035-s3tkbh9r 92 1 In in IN cord-311035-s3tkbh9r 92 2 this this DT cord-311035-s3tkbh9r 92 3 way way NN cord-311035-s3tkbh9r 92 4 , , , cord-311035-s3tkbh9r 92 5 information information NN cord-311035-s3tkbh9r 92 6 was be VBD cord-311035-s3tkbh9r 92 7 collected collect VBN cord-311035-s3tkbh9r 92 8 on on IN cord-311035-s3tkbh9r 92 9 how how WRB cord-311035-s3tkbh9r 92 10 ACE2 ACE2 NNP cord-311035-s3tkbh9r 92 11 mutations mutation NNS cord-311035-s3tkbh9r 92 12 impact impact NN cord-311035-s3tkbh9r 92 13 expression expression NN cord-311035-s3tkbh9r 92 14 and and CC cord-311035-s3tkbh9r 92 15 RBD rbd NN cord-311035-s3tkbh9r 92 16 binding bind VBG cord-311035-s3tkbh9r 92 17 from from IN cord-311035-s3tkbh9r 92 18 a a DT cord-311035-s3tkbh9r 92 19 single single JJ cord-311035-s3tkbh9r 92 20 FACS FACS NNP cord-311035-s3tkbh9r 92 21 experiment experiment NN cord-311035-s3tkbh9r 92 22 . . . cord-311035-s3tkbh9r 93 1 The the DT cord-311035-s3tkbh9r 93 2 deep deep JJ cord-311035-s3tkbh9r 93 3 mutational mutational JJ cord-311035-s3tkbh9r 93 4 scan scan NN cord-311035-s3tkbh9r 93 5 of of IN cord-311035-s3tkbh9r 93 6 ACE2 ACE2 NNP cord-311035-s3tkbh9r 93 7 revealed reveal VBD cord-311035-s3tkbh9r 93 8 that that IN cord-311035-s3tkbh9r 93 9 mutations mutation NNS cord-311035-s3tkbh9r 93 10 can can MD cord-311035-s3tkbh9r 93 11 indeed indeed RB cord-311035-s3tkbh9r 93 12 be be VB cord-311035-s3tkbh9r 93 13 found find VBN cord-311035-s3tkbh9r 93 14 to to TO cord-311035-s3tkbh9r 93 15 enhance enhance VB cord-311035-s3tkbh9r 93 16 binding binding NN cord-311035-s3tkbh9r 93 17 toward toward IN cord-311035-s3tkbh9r 93 18 SARS SARS NNP cord-311035-s3tkbh9r 93 19 - - HYPH cord-311035-s3tkbh9r 93 20 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 93 21 RBD RBD NNP cord-311035-s3tkbh9r 93 22 ( ( -LRB- cord-311035-s3tkbh9r 93 23 Figure figure NN cord-311035-s3tkbh9r 93 24 2 2 CD cord-311035-s3tkbh9r 93 25 ) ) -RRB- cord-311035-s3tkbh9r 93 26 , , , cord-311035-s3tkbh9r 93 27 suitable suitable JJ cord-311035-s3tkbh9r 93 28 for for IN cord-311035-s3tkbh9r 93 29 engineering engineer VBG cord-311035-s3tkbh9r 93 30 high high JJ cord-311035-s3tkbh9r 93 31 affinity affinity NN cord-311035-s3tkbh9r 93 32 soluble soluble JJ cord-311035-s3tkbh9r 93 33 decoy decoy NN cord-311035-s3tkbh9r 93 34 receptors receptor NNS cord-311035-s3tkbh9r 93 35 [ [ -LRB- cord-311035-s3tkbh9r 93 36 15 15 CD cord-311035-s3tkbh9r 93 37 ] ] -RRB- cord-311035-s3tkbh9r 93 38 . . . cord-311035-s3tkbh9r 94 1 Mutations mutation NNS cord-311035-s3tkbh9r 94 2 were be VBD cord-311035-s3tkbh9r 94 3 found find VBN cord-311035-s3tkbh9r 94 4 at at IN cord-311035-s3tkbh9r 94 5 the the DT cord-311035-s3tkbh9r 94 6 binding bind VBG cord-311035-s3tkbh9r 94 7 interface interface NN cord-311035-s3tkbh9r 94 8 where where WRB cord-311035-s3tkbh9r 94 9 they -PRON- PRP cord-311035-s3tkbh9r 94 10 enhance enhance VBP cord-311035-s3tkbh9r 94 11 specific specific JJ cord-311035-s3tkbh9r 94 12 atomic atomic JJ cord-311035-s3tkbh9r 94 13 contacts contact NNS cord-311035-s3tkbh9r 94 14 , , , cord-311035-s3tkbh9r 94 15 and and CC cord-311035-s3tkbh9r 94 16 were be VBD cord-311035-s3tkbh9r 94 17 also also RB cord-311035-s3tkbh9r 94 18 found find VBN cord-311035-s3tkbh9r 94 19 distally distally RB cord-311035-s3tkbh9r 94 20 in in IN cord-311035-s3tkbh9r 94 21 the the DT cord-311035-s3tkbh9r 94 22 second second JJ cord-311035-s3tkbh9r 94 23 shell shell NN cord-311035-s3tkbh9r 94 24 and and CC cord-311035-s3tkbh9r 94 25 beyond beyond IN cord-311035-s3tkbh9r 94 26 where where WRB cord-311035-s3tkbh9r 94 27 they -PRON- PRP cord-311035-s3tkbh9r 94 28 may may MD cord-311035-s3tkbh9r 94 29 impact impact VB cord-311035-s3tkbh9r 94 30 ACE2 ACE2 NNP cord-311035-s3tkbh9r 94 31 conformation conformation NN cord-311035-s3tkbh9r 94 32 , , , cord-311035-s3tkbh9r 94 33 folding folding NN cord-311035-s3tkbh9r 94 34 and and CC cord-311035-s3tkbh9r 94 35 dynamics dynamic NNS cord-311035-s3tkbh9r 94 36 . . . cord-311035-s3tkbh9r 95 1 A a DT cord-311035-s3tkbh9r 95 2 soluble soluble JJ cord-311035-s3tkbh9r 95 3 ACE2 ACE2 NNP cord-311035-s3tkbh9r 95 4 variant variant NN cord-311035-s3tkbh9r 95 5 that that WDT cord-311035-s3tkbh9r 95 6 combines combine VBZ cord-311035-s3tkbh9r 95 7 three three CD cord-311035-s3tkbh9r 95 8 mutations mutation NNS cord-311035-s3tkbh9r 95 9 , , , cord-311035-s3tkbh9r 95 10 called call VBD cord-311035-s3tkbh9r 95 11 sACE2 sACE2 NNP cord-311035-s3tkbh9r 95 12 2 2 CD cord-311035-s3tkbh9r 95 13 .v2.4 .v2.4 NFP cord-311035-s3tkbh9r 95 14 , , , cord-311035-s3tkbh9r 95 15 was be VBD cord-311035-s3tkbh9r 95 16 found find VBN cord-311035-s3tkbh9r 95 17 to to TO cord-311035-s3tkbh9r 95 18 be be VB cord-311035-s3tkbh9r 95 19 highly highly RB cord-311035-s3tkbh9r 95 20 expressed express VBN cord-311035-s3tkbh9r 95 21 , , , cord-311035-s3tkbh9r 95 22 is be VBZ cord-311035-s3tkbh9r 95 23 a a DT cord-311035-s3tkbh9r 95 24 stable stable JJ cord-311035-s3tkbh9r 95 25 monodisperse monodisperse NNP cord-311035-s3tkbh9r 95 26 dimer dimer NN cord-311035-s3tkbh9r 95 27 , , , cord-311035-s3tkbh9r 95 28 binds bind VBZ cord-311035-s3tkbh9r 95 29 SARS SARS NNP cord-311035-s3tkbh9r 95 30 - - HYPH cord-311035-s3tkbh9r 95 31 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 95 32 S S NNP cord-311035-s3tkbh9r 95 33 with with IN cord-311035-s3tkbh9r 95 34 picomolar picomolar JJ cord-311035-s3tkbh9r 95 35 affinity affinity NN cord-311035-s3tkbh9r 95 36 and and CC cord-311035-s3tkbh9r 95 37 potently potently RB cord-311035-s3tkbh9r 95 38 neutralizes neutralize VBZ cord-311035-s3tkbh9r 95 39 infection infection NN cord-311035-s3tkbh9r 95 40 of of IN cord-311035-s3tkbh9r 95 41 a a DT cord-311035-s3tkbh9r 95 42 susceptible susceptible JJ cord-311035-s3tkbh9r 95 43 cell cell NN cord-311035-s3tkbh9r 95 44 line line NN cord-311035-s3tkbh9r 95 45 by by IN cord-311035-s3tkbh9r 95 46 authentic authentic JJ cord-311035-s3tkbh9r 95 47 virus virus NN cord-311035-s3tkbh9r 95 48 . . . cord-311035-s3tkbh9r 96 1 Its -PRON- PRP$ cord-311035-s3tkbh9r 96 2 properties property NNS cord-311035-s3tkbh9r 96 3 rival rival JJ cord-311035-s3tkbh9r 96 4 affinity affinity NN cord-311035-s3tkbh9r 96 5 - - HYPH cord-311035-s3tkbh9r 96 6 matured mature VBN cord-311035-s3tkbh9r 96 7 monoclonal monoclonal JJ cord-311035-s3tkbh9r 96 8 antibodies antibody NNS cord-311035-s3tkbh9r 96 9 under under IN cord-311035-s3tkbh9r 96 10 commercial commercial JJ cord-311035-s3tkbh9r 96 11 development development NN cord-311035-s3tkbh9r 96 12 for for IN cord-311035-s3tkbh9r 96 13 therapy therapy NN cord-311035-s3tkbh9r 96 14 and and CC cord-311035-s3tkbh9r 96 15 prophylaxis prophylaxis NN cord-311035-s3tkbh9r 96 16 . . . cord-311035-s3tkbh9r 97 1 Despite despite IN cord-311035-s3tkbh9r 97 2 only only JJ cord-311035-s3tkbh9r 97 3 affinity affinity NN cord-311035-s3tkbh9r 97 4 toward toward IN cord-311035-s3tkbh9r 97 5 SARS SARS NNP cord-311035-s3tkbh9r 97 6 - - HYPH cord-311035-s3tkbh9r 97 7 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 97 8 being be VBG cord-311035-s3tkbh9r 97 9 considered consider VBN cord-311035-s3tkbh9r 97 10 during during IN cord-311035-s3tkbh9r 97 11 the the DT cord-311035-s3tkbh9r 97 12 engineering engineering NN cord-311035-s3tkbh9r 97 13 process process NN cord-311035-s3tkbh9r 97 14 , , , cord-311035-s3tkbh9r 97 15 sACE2 sACE2 NNP cord-311035-s3tkbh9r 97 16 2 2 CD cord-311035-s3tkbh9r 97 17 . . . cord-311035-s3tkbh9r 97 18 v2.4 v2.4 NNP cord-311035-s3tkbh9r 97 19 also also RB cord-311035-s3tkbh9r 97 20 potently potently RB cord-311035-s3tkbh9r 97 21 neutralizes neutralize VBZ cord-311035-s3tkbh9r 97 22 authentic authentic JJ cord-311035-s3tkbh9r 97 23 SARS SARS NNP cord-311035-s3tkbh9r 97 24 - - HYPH cord-311035-s3tkbh9r 97 25 CoV-1 CoV-1 NNP cord-311035-s3tkbh9r 97 26 , , , cord-311035-s3tkbh9r 97 27 and and CC cord-311035-s3tkbh9r 97 28 we -PRON- PRP cord-311035-s3tkbh9r 97 29 speculate speculate VBP cord-311035-s3tkbh9r 97 30 that that IN cord-311035-s3tkbh9r 97 31 it -PRON- PRP cord-311035-s3tkbh9r 97 32 will will MD cord-311035-s3tkbh9r 97 33 have have VB cord-311035-s3tkbh9r 97 34 broad broad JJ cord-311035-s3tkbh9r 97 35 activity activity NN cord-311035-s3tkbh9r 97 36 against against IN cord-311035-s3tkbh9r 97 37 betacoronaviruses betacoronaviruse NNS cord-311035-s3tkbh9r 97 38 that that WDT cord-311035-s3tkbh9r 97 39 use use VBP cord-311035-s3tkbh9r 97 40 ACE2 ACE2 NNP cord-311035-s3tkbh9r 97 41 as as IN cord-311035-s3tkbh9r 97 42 an an DT cord-311035-s3tkbh9r 97 43 entry entry NN cord-311035-s3tkbh9r 97 44 receptor receptor NN cord-311035-s3tkbh9r 97 45 . . . cord-311035-s3tkbh9r 98 1 In in IN cord-311035-s3tkbh9r 98 2 unpublished unpublished JJ cord-311035-s3tkbh9r 98 3 work work NN cord-311035-s3tkbh9r 98 4 that that WDT cord-311035-s3tkbh9r 98 5 has have VBZ cord-311035-s3tkbh9r 98 6 yet yet RB cord-311035-s3tkbh9r 98 7 to to TO cord-311035-s3tkbh9r 98 8 be be VB cord-311035-s3tkbh9r 98 9 peer peer NN cord-311035-s3tkbh9r 98 10 reviewed review VBN cord-311035-s3tkbh9r 98 11 , , , cord-311035-s3tkbh9r 98 12 we -PRON- PRP cord-311035-s3tkbh9r 98 13 have have VBP cord-311035-s3tkbh9r 98 14 found find VBN cord-311035-s3tkbh9r 98 15 sACE2 sACE2 NNP cord-311035-s3tkbh9r 98 16 2 2 CD cord-311035-s3tkbh9r 98 17 . . . cord-311035-s3tkbh9r 99 1 v2.4 v2.4 NNP cord-311035-s3tkbh9r 99 2 broadly broadly RB cord-311035-s3tkbh9r 99 3 and and CC cord-311035-s3tkbh9r 99 4 tightly tightly RB cord-311035-s3tkbh9r 99 5 binds bind VBZ cord-311035-s3tkbh9r 99 6 bat bat NN cord-311035-s3tkbh9r 99 7 coronaviruses coronaviruse NNS cord-311035-s3tkbh9r 99 8 that that WDT cord-311035-s3tkbh9r 99 9 may may MD cord-311035-s3tkbh9r 99 10 be be VB cord-311035-s3tkbh9r 99 11 a a DT cord-311035-s3tkbh9r 99 12 source source NN cord-311035-s3tkbh9r 99 13 for for IN cord-311035-s3tkbh9r 99 14 future future JJ cord-311035-s3tkbh9r 99 15 pandemics pandemic NNS cord-311035-s3tkbh9r 99 16 , , , cord-311035-s3tkbh9r 99 17 supporting support VBG cord-311035-s3tkbh9r 99 18 the the DT cord-311035-s3tkbh9r 99 19 concept concept NN cord-311035-s3tkbh9r 99 20 of of IN cord-311035-s3tkbh9r 99 21 receptor receptor NN cord-311035-s3tkbh9r 99 22 - - HYPH cord-311035-s3tkbh9r 99 23 based base VBN cord-311035-s3tkbh9r 99 24 decoys decoy NNS cord-311035-s3tkbh9r 99 25 as as IN cord-311035-s3tkbh9r 99 26 antiviral antiviral JJ cord-311035-s3tkbh9r 99 27 biologics biologic NNS cord-311035-s3tkbh9r 99 28 with with IN cord-311035-s3tkbh9r 99 29 exceptional exceptional JJ cord-311035-s3tkbh9r 99 30 breadth breadth NN cord-311035-s3tkbh9r 99 31 . . . cord-311035-s3tkbh9r 100 1 As as IN cord-311035-s3tkbh9r 100 2 determined determine VBN cord-311035-s3tkbh9r 100 3 by by IN cord-311035-s3tkbh9r 100 4 yeast yeast NN cord-311035-s3tkbh9r 100 5 display display NN cord-311035-s3tkbh9r 100 6 , , , cord-311035-s3tkbh9r 100 7 the the DT cord-311035-s3tkbh9r 100 8 effects effect NNS cord-311035-s3tkbh9r 100 9 of of IN cord-311035-s3tkbh9r 100 10 mutations mutation NNS cord-311035-s3tkbh9r 100 11 in in IN cord-311035-s3tkbh9r 100 12 the the DT cord-311035-s3tkbh9r 100 13 RBD RBD NNP cord-311035-s3tkbh9r 100 14 of of IN cord-311035-s3tkbh9r 100 15 SARS SARS NNP cord-311035-s3tkbh9r 100 16 - - HYPH cord-311035-s3tkbh9r 100 17 COV-2 COV-2 NNP cord-311035-s3tkbh9r 100 18 protein protein NN cord-311035-s3tkbh9r 100 19 S S NNP cord-311035-s3tkbh9r 100 20 on on IN cord-311035-s3tkbh9r 100 21 receptor receptor NN cord-311035-s3tkbh9r 100 22 affinity affinity NN cord-311035-s3tkbh9r 100 23 are be VBP cord-311035-s3tkbh9r 100 24 plotted plot VBN cord-311035-s3tkbh9r 100 25 in in IN cord-311035-s3tkbh9r 100 26 the the DT cord-311035-s3tkbh9r 100 27 heat heat NN cord-311035-s3tkbh9r 100 28 map map NN cord-311035-s3tkbh9r 100 29 at at IN cord-311035-s3tkbh9r 100 30 left left NN cord-311035-s3tkbh9r 100 31 , , , cord-311035-s3tkbh9r 100 32 with with IN cord-311035-s3tkbh9r 100 33 dark dark JJ cord-311035-s3tkbh9r 100 34 green green JJ cord-311035-s3tkbh9r 100 35 indicating indicate VBG cord-311035-s3tkbh9r 100 36 the the DT cord-311035-s3tkbh9r 100 37 mutations mutation NNS cord-311035-s3tkbh9r 100 38 are be VBP cord-311035-s3tkbh9r 100 39 deleterious deleterious JJ cord-311035-s3tkbh9r 100 40 and and CC cord-311035-s3tkbh9r 100 41 pale pale JJ cord-311035-s3tkbh9r 100 42 colors color NNS cord-311035-s3tkbh9r 100 43 indicating indicate VBG cord-311035-s3tkbh9r 100 44 the the DT cord-311035-s3tkbh9r 100 45 mutations mutation NNS cord-311035-s3tkbh9r 100 46 are be VBP cord-311035-s3tkbh9r 100 47 neutral neutral JJ cord-311035-s3tkbh9r 100 48 . . . cord-311035-s3tkbh9r 101 1 The the DT cord-311035-s3tkbh9r 101 2 effects effect NNS cord-311035-s3tkbh9r 101 3 of of IN cord-311035-s3tkbh9r 101 4 mutations mutation NNS cord-311035-s3tkbh9r 101 5 in in IN cord-311035-s3tkbh9r 101 6 human human JJ cord-311035-s3tkbh9r 101 7 cell cell NN cord-311035-s3tkbh9r 101 8 - - : cord-311035-s3tkbh9r 101 9 expressed express VBN cord-311035-s3tkbh9r 101 10 ACE2 ACE2 NNP cord-311035-s3tkbh9r 101 11 on on IN cord-311035-s3tkbh9r 101 12 binding bind VBG cord-311035-s3tkbh9r 101 13 to to IN cord-311035-s3tkbh9r 101 14 soluble soluble JJ cord-311035-s3tkbh9r 101 15 RBD RBD NNP cord-311035-s3tkbh9r 101 16 are be VBP cord-311035-s3tkbh9r 101 17 plotted plot VBN cord-311035-s3tkbh9r 101 18 in in IN cord-311035-s3tkbh9r 101 19 the the DT cord-311035-s3tkbh9r 101 20 heat heat NN cord-311035-s3tkbh9r 101 21 map map NN cord-311035-s3tkbh9r 101 22 at at IN cord-311035-s3tkbh9r 101 23 right right NN cord-311035-s3tkbh9r 101 24 , , , cord-311035-s3tkbh9r 101 25 with with IN cord-311035-s3tkbh9r 101 26 depleted depleted JJ cord-311035-s3tkbh9r 101 27 mutations mutation NNS cord-311035-s3tkbh9r 101 28 in in IN cord-311035-s3tkbh9r 101 29 orange orange JJ cord-311035-s3tkbh9r 101 30 , , , cord-311035-s3tkbh9r 101 31 neutral neutral JJ cord-311035-s3tkbh9r 101 32 mutations mutation NNS cord-311035-s3tkbh9r 101 33 in in IN cord-311035-s3tkbh9r 101 34 white white JJ cord-311035-s3tkbh9r 101 35 and and CC cord-311035-s3tkbh9r 101 36 enriched enriched JJ cord-311035-s3tkbh9r 101 37 mutations mutation NNS cord-311035-s3tkbh9r 101 38 in in IN cord-311035-s3tkbh9r 101 39 blue blue NN cord-311035-s3tkbh9r 101 40 . . . cord-311035-s3tkbh9r 102 1 Positional positional JJ cord-311035-s3tkbh9r 102 2 scores score NNS cord-311035-s3tkbh9r 102 3 are be VBP cord-311035-s3tkbh9r 102 4 mapped map VBN cord-311035-s3tkbh9r 102 5 to to IN cord-311035-s3tkbh9r 102 6 the the DT cord-311035-s3tkbh9r 102 7 atomic atomic JJ cord-311035-s3tkbh9r 102 8 structure structure NN cord-311035-s3tkbh9r 102 9 of of IN cord-311035-s3tkbh9r 102 10 RBD RBD NNP cord-311035-s3tkbh9r 102 11 - - HYPH cord-311035-s3tkbh9r 102 12 bound bind VBN cord-311035-s3tkbh9r 102 13 ACE2 ACE2 NNP cord-311035-s3tkbh9r 102 14 ( ( -LRB- cord-311035-s3tkbh9r 102 15 PDB PDB NNP cord-311035-s3tkbh9r 102 16 6M17 6m17 CD cord-311035-s3tkbh9r 102 17 ) ) -RRB- cord-311035-s3tkbh9r 102 18 at at IN cord-311035-s3tkbh9r 102 19 center center NN cord-311035-s3tkbh9r 102 20 . . . cord-311035-s3tkbh9r 103 1 Conserved conserved JJ cord-311035-s3tkbh9r 103 2 ACE2 ACE2 NNP cord-311035-s3tkbh9r 103 3 residues residue NNS cord-311035-s3tkbh9r 103 4 for for IN cord-311035-s3tkbh9r 103 5 RBD RBD NNP cord-311035-s3tkbh9r 103 6 binding binding NN cord-311035-s3tkbh9r 103 7 are be VBP cord-311035-s3tkbh9r 103 8 orange orange JJ cord-311035-s3tkbh9r 103 9 , , , cord-311035-s3tkbh9r 103 10 while while IN cord-311035-s3tkbh9r 103 11 ACE2 ACE2 NNP cord-311035-s3tkbh9r 103 12 residues residue NNS cord-311035-s3tkbh9r 103 13 that that WDT cord-311035-s3tkbh9r 103 14 are be VBP cord-311035-s3tkbh9r 103 15 hot hot JJ cord-311035-s3tkbh9r 103 16 spots spot NNS cord-311035-s3tkbh9r 103 17 for for IN cord-311035-s3tkbh9r 103 18 mutations mutation NNS cord-311035-s3tkbh9r 103 19 with with IN cord-311035-s3tkbh9r 103 20 increased increase VBN cord-311035-s3tkbh9r 103 21 affinity affinity NN cord-311035-s3tkbh9r 103 22 are be VBP cord-311035-s3tkbh9r 103 23 blue blue JJ cord-311035-s3tkbh9r 103 24 . . . cord-311035-s3tkbh9r 104 1 RBD RBD NNP cord-311035-s3tkbh9r 104 2 residues residue NNS cord-311035-s3tkbh9r 104 3 conserved conserve VBN cord-311035-s3tkbh9r 104 4 for for IN cord-311035-s3tkbh9r 104 5 ACE2 ACE2 NNP cord-311035-s3tkbh9r 104 6 binding binding NN cord-311035-s3tkbh9r 104 7 are be VBP cord-311035-s3tkbh9r 104 8 green green JJ cord-311035-s3tkbh9r 104 9 . . . cord-311035-s3tkbh9r 105 1 Most Most JJS cord-311035-s3tkbh9r 105 2 RBD RBD NNP cord-311035-s3tkbh9r 105 3 mutations mutation NNS cord-311035-s3tkbh9r 105 4 in in IN cord-311035-s3tkbh9r 105 5 this this DT cord-311035-s3tkbh9r 105 6 region region NN cord-311035-s3tkbh9r 105 7 of of IN cord-311035-s3tkbh9r 105 8 the the DT cord-311035-s3tkbh9r 105 9 interface interface NN cord-311035-s3tkbh9r 105 10 are be VBP cord-311035-s3tkbh9r 105 11 deleterious deleterious JJ cord-311035-s3tkbh9r 105 12 , , , cord-311035-s3tkbh9r 105 13 whereas whereas IN cord-311035-s3tkbh9r 105 14 numerous numerous JJ cord-311035-s3tkbh9r 105 15 mutations mutation NNS cord-311035-s3tkbh9r 105 16 were be VBD cord-311035-s3tkbh9r 105 17 found find VBN cord-311035-s3tkbh9r 105 18 in in IN cord-311035-s3tkbh9r 105 19 ACE2 ACE2 NNP cord-311035-s3tkbh9r 105 20 that that WDT cord-311035-s3tkbh9r 105 21 increased increase VBD cord-311035-s3tkbh9r 105 22 affinity affinity NN cord-311035-s3tkbh9r 105 23 . . . cord-311035-s3tkbh9r 106 1 In in IN cord-311035-s3tkbh9r 106 2 Starr Starr NNP cord-311035-s3tkbh9r 106 3 et et NNP cord-311035-s3tkbh9r 106 4 al al NNP cord-311035-s3tkbh9r 106 5 , , , cord-311035-s3tkbh9r 106 6 deep deep JJ cord-311035-s3tkbh9r 106 7 mutagenesis mutagenesis NN cord-311035-s3tkbh9r 106 8 was be VBD cord-311035-s3tkbh9r 106 9 applied apply VBN cord-311035-s3tkbh9r 106 10 to to IN cord-311035-s3tkbh9r 106 11 the the DT cord-311035-s3tkbh9r 106 12 SARS SARS NNP cord-311035-s3tkbh9r 106 13 - - HYPH cord-311035-s3tkbh9r 106 14 CoV CoV NNP cord-311035-s3tkbh9r 106 15 -2 -2 NN cord-311035-s3tkbh9r 106 16 spike spike NN cord-311035-s3tkbh9r 106 17 to to TO cord-311035-s3tkbh9r 106 18 assess assess VB cord-311035-s3tkbh9r 106 19 mutational mutational JJ cord-311035-s3tkbh9r 106 20 tolerance tolerance NN cord-311035-s3tkbh9r 106 21 for for IN cord-311035-s3tkbh9r 106 22 expression expression NN cord-311035-s3tkbh9r 106 23 and and CC cord-311035-s3tkbh9r 106 24 ACE2 ACE2 NNP cord-311035-s3tkbh9r 106 25 interactions interaction NNS cord-311035-s3tkbh9r 106 26 [ [ -LRB- cord-311035-s3tkbh9r 106 27 14 14 CD cord-311035-s3tkbh9r 106 28 ] ] -RRB- cord-311035-s3tkbh9r 106 29 . . . cord-311035-s3tkbh9r 107 1 Instead instead RB cord-311035-s3tkbh9r 107 2 of of IN cord-311035-s3tkbh9r 107 3 investigating investigate VBG cord-311035-s3tkbh9r 107 4 the the DT cord-311035-s3tkbh9r 107 5 entire entire JJ cord-311035-s3tkbh9r 107 6 trimeric trimeric NNP cord-311035-s3tkbh9r 107 7 S S NNP cord-311035-s3tkbh9r 107 8 protein protein NN cord-311035-s3tkbh9r 107 9 expressed express VBD cord-311035-s3tkbh9r 107 10 on on IN cord-311035-s3tkbh9r 107 11 a a DT cord-311035-s3tkbh9r 107 12 cellular cellular JJ cord-311035-s3tkbh9r 107 13 or or CC cord-311035-s3tkbh9r 107 14 viral viral JJ cord-311035-s3tkbh9r 107 15 membrane membrane NN cord-311035-s3tkbh9r 107 16 , , , cord-311035-s3tkbh9r 107 17 the the DT cord-311035-s3tkbh9r 107 18 isolated isolated JJ cord-311035-s3tkbh9r 107 19 RBD RBD NNP cord-311035-s3tkbh9r 107 20 was be VBD cord-311035-s3tkbh9r 107 21 fused fuse VBN cord-311035-s3tkbh9r 107 22 to to IN cord-311035-s3tkbh9r 107 23 the the DT cord-311035-s3tkbh9r 107 24 yeast yeast NN cord-311035-s3tkbh9r 107 25 mating mating NN cord-311035-s3tkbh9r 107 26 factor factor NN cord-311035-s3tkbh9r 107 27 Aga2p Aga2p NNP cord-311035-s3tkbh9r 107 28 and and CC cord-311035-s3tkbh9r 107 29 displayed display VBD cord-311035-s3tkbh9r 107 30 on on IN cord-311035-s3tkbh9r 107 31 the the DT cord-311035-s3tkbh9r 107 32 yeast yeast NN cord-311035-s3tkbh9r 107 33 surface surface NN cord-311035-s3tkbh9r 107 34 [ [ -LRB- cord-311035-s3tkbh9r 107 35 53 53 CD cord-311035-s3tkbh9r 107 36 ] ] -RRB- cord-311035-s3tkbh9r 107 37 ( ( -LRB- cord-311035-s3tkbh9r 107 38 Figure figure NN cord-311035-s3tkbh9r 107 39 1B 1b CD cord-311035-s3tkbh9r 107 40 ) ) -RRB- cord-311035-s3tkbh9r 107 41 . . . cord-311035-s3tkbh9r 108 1 This this DT cord-311035-s3tkbh9r 108 2 is be VBZ cord-311035-s3tkbh9r 108 3 an an DT cord-311035-s3tkbh9r 108 4 artificial artificial JJ cord-311035-s3tkbh9r 108 5 display display NN cord-311035-s3tkbh9r 108 6 platform platform NN cord-311035-s3tkbh9r 108 7 that that WDT cord-311035-s3tkbh9r 108 8 removes remove VBZ cord-311035-s3tkbh9r 108 9 the the DT cord-311035-s3tkbh9r 108 10 RBD RBD NNP cord-311035-s3tkbh9r 108 11 from from IN cord-311035-s3tkbh9r 108 12 its -PRON- PRP$ cord-311035-s3tkbh9r 108 13 native native JJ cord-311035-s3tkbh9r 108 14 context context NN cord-311035-s3tkbh9r 108 15 . . . cord-311035-s3tkbh9r 109 1 N N NNP cord-311035-s3tkbh9r 109 2 - - HYPH cord-311035-s3tkbh9r 109 3 Glycosylation Glycosylation NNP cord-311035-s3tkbh9r 109 4 in in IN cord-311035-s3tkbh9r 109 5 yeast yeast NN cord-311035-s3tkbh9r 109 6 is be VBZ cord-311035-s3tkbh9r 109 7 also also RB cord-311035-s3tkbh9r 109 8 of of IN cord-311035-s3tkbh9r 109 9 high high JJ cord-311035-s3tkbh9r 109 10 - - HYPH cord-311035-s3tkbh9r 109 11 mannose mannose NN cord-311035-s3tkbh9r 109 12 type type NN cord-311035-s3tkbh9r 109 13 and and CC cord-311035-s3tkbh9r 109 14 lacks lack VBZ cord-311035-s3tkbh9r 109 15 the the DT cord-311035-s3tkbh9r 109 16 complex complex JJ cord-311035-s3tkbh9r 109 17 , , , cord-311035-s3tkbh9r 109 18 terminally terminally RB cord-311035-s3tkbh9r 109 19 sialylated sialylate VBN cord-311035-s3tkbh9r 109 20 glycans glycan NNS cord-311035-s3tkbh9r 109 21 produced produce VBN cord-311035-s3tkbh9r 109 22 by by IN cord-311035-s3tkbh9r 109 23 human human JJ cord-311035-s3tkbh9r 109 24 cells cell NNS cord-311035-s3tkbh9r 109 25 [ [ -LRB- cord-311035-s3tkbh9r 109 26 54 54 CD cord-311035-s3tkbh9r 109 27 ] ] -RRB- cord-311035-s3tkbh9r 109 28 , , , cord-311035-s3tkbh9r 109 29 which which WDT cord-311035-s3tkbh9r 109 30 can can MD cord-311035-s3tkbh9r 109 31 be be VB cord-311035-s3tkbh9r 109 32 important important JJ cord-311035-s3tkbh9r 109 33 when when WRB cord-311035-s3tkbh9r 109 34 binding bind VBG cord-311035-s3tkbh9r 109 35 interactions interaction NNS cord-311035-s3tkbh9r 109 36 are be VBP cord-311035-s3tkbh9r 109 37 glycan glycan NN cord-311035-s3tkbh9r 109 38 - - HYPH cord-311035-s3tkbh9r 109 39 dependent dependent JJ cord-311035-s3tkbh9r 109 40 as as IN cord-311035-s3tkbh9r 109 41 is be VBZ cord-311035-s3tkbh9r 109 42 seen see VBN cord-311035-s3tkbh9r 109 43 for for IN cord-311035-s3tkbh9r 109 44 some some DT cord-311035-s3tkbh9r 109 45 antibodies antibody NNS cord-311035-s3tkbh9r 109 46 targeting target VBG cord-311035-s3tkbh9r 109 47 viral viral JJ cord-311035-s3tkbh9r 109 48 spikes spike NNS cord-311035-s3tkbh9r 109 49 [ [ -LRB- cord-311035-s3tkbh9r 109 50 55 55 CD cord-311035-s3tkbh9r 109 51 ] ] -RRB- cord-311035-s3tkbh9r 109 52 . . . cord-311035-s3tkbh9r 110 1 However however RB cord-311035-s3tkbh9r 110 2 , , , cord-311035-s3tkbh9r 110 3 this this DT cord-311035-s3tkbh9r 110 4 display display NN cord-311035-s3tkbh9r 110 5 platform platform NN cord-311035-s3tkbh9r 110 6 harnesses harness VBZ cord-311035-s3tkbh9r 110 7 yeast yeast NN cord-311035-s3tkbh9r 110 8 genetics genetic NNS cord-311035-s3tkbh9r 110 9 to to TO cord-311035-s3tkbh9r 110 10 confer confer VB cord-311035-s3tkbh9r 110 11 tremendous tremendous JJ cord-311035-s3tkbh9r 110 12 advantages advantage NNS cord-311035-s3tkbh9r 110 13 for for IN cord-311035-s3tkbh9r 110 14 in in FW cord-311035-s3tkbh9r 110 15 vitro vitro FW cord-311035-s3tkbh9r 110 16 selection selection NN cord-311035-s3tkbh9r 110 17 and and CC cord-311035-s3tkbh9r 110 18 evolution evolution NN cord-311035-s3tkbh9r 110 19 . . . cord-311035-s3tkbh9r 111 1 Using use VBG cord-311035-s3tkbh9r 111 2 yeast yeast NN cord-311035-s3tkbh9r 111 3 display display NN cord-311035-s3tkbh9r 111 4 , , , cord-311035-s3tkbh9r 111 5 large large JJ cord-311035-s3tkbh9r 111 6 diverse diverse JJ cord-311035-s3tkbh9r 111 7 libraries library NNS cord-311035-s3tkbh9r 111 8 can can MD cord-311035-s3tkbh9r 111 9 be be VB cord-311035-s3tkbh9r 111 10 readily readily RB cord-311035-s3tkbh9r 111 11 sorted sort VBN cord-311035-s3tkbh9r 111 12 by by IN cord-311035-s3tkbh9r 111 13 FACS FACS NNP cord-311035-s3tkbh9r 111 14 to to TO cord-311035-s3tkbh9r 111 15 provide provide VB cord-311035-s3tkbh9r 111 16 highquality highquality JJ cord-311035-s3tkbh9r 111 17 data datum NNS cord-311035-s3tkbh9r 111 18 . . . cord-311035-s3tkbh9r 112 1 Separate separate JJ cord-311035-s3tkbh9r 112 2 selections selection NNS cord-311035-s3tkbh9r 112 3 were be VBD cord-311035-s3tkbh9r 112 4 completed complete VBN cord-311035-s3tkbh9r 112 5 at at IN cord-311035-s3tkbh9r 112 6 a a DT cord-311035-s3tkbh9r 112 7 range range NN cord-311035-s3tkbh9r 112 8 of of IN cord-311035-s3tkbh9r 112 9 different different JJ cord-311035-s3tkbh9r 112 10 sACE2 sace2 NN cord-311035-s3tkbh9r 112 11 concentrations concentration NNS cord-311035-s3tkbh9r 112 12 to to TO cord-311035-s3tkbh9r 112 13 simulate simulate VB cord-311035-s3tkbh9r 112 14 a a DT cord-311035-s3tkbh9r 112 15 titration titration NN cord-311035-s3tkbh9r 112 16 experiment experiment NN cord-311035-s3tkbh9r 112 17 , , , cord-311035-s3tkbh9r 112 18 from from IN cord-311035-s3tkbh9r 112 19 which which WDT cord-311035-s3tkbh9r 112 20 the the DT cord-311035-s3tkbh9r 112 21 data datum NNS cord-311035-s3tkbh9r 112 22 could could MD cord-311035-s3tkbh9r 112 23 be be VB cord-311035-s3tkbh9r 112 24 converted convert VBN cord-311035-s3tkbh9r 112 25 to to IN cord-311035-s3tkbh9r 112 26 quantitative quantitative JJ cord-311035-s3tkbh9r 112 27 changes change NNS cord-311035-s3tkbh9r 112 28 in in IN cord-311035-s3tkbh9r 112 29 apparent apparent JJ cord-311035-s3tkbh9r 112 30 K k NN cord-311035-s3tkbh9r 112 31 D D NNP cord-311035-s3tkbh9r 112 32 on on IN cord-311035-s3tkbh9r 112 33 the the DT cord-311035-s3tkbh9r 112 34 yeast yeast NN cord-311035-s3tkbh9r 112 35 surface surface NN cord-311035-s3tkbh9r 112 36 ( ( -LRB- cord-311035-s3tkbh9r 112 37 Figure figure NN cord-311035-s3tkbh9r 112 38 2 2 CD cord-311035-s3tkbh9r 112 39 ) ) -RRB- cord-311035-s3tkbh9r 112 40 . . . cord-311035-s3tkbh9r 113 1 As as IN cord-311035-s3tkbh9r 113 2 a a DT cord-311035-s3tkbh9r 113 3 surrogate surrogate NN cord-311035-s3tkbh9r 113 4 for for IN cord-311035-s3tkbh9r 113 5 how how WRB cord-311035-s3tkbh9r 113 6 RBD RBD NNP cord-311035-s3tkbh9r 113 7 mutations mutation NNS cord-311035-s3tkbh9r 113 8 may may MD cord-311035-s3tkbh9r 113 9 impact impact VB cord-311035-s3tkbh9r 113 10 expression expression NN cord-311035-s3tkbh9r 113 11 of of IN cord-311035-s3tkbh9r 113 12 the the DT cord-311035-s3tkbh9r 113 13 viral viral JJ cord-311035-s3tkbh9r 113 14 spike spike NN cord-311035-s3tkbh9r 113 15 , , , cord-311035-s3tkbh9r 113 16 the the DT cord-311035-s3tkbh9r 113 17 effects effect NNS cord-311035-s3tkbh9r 113 18 of of IN cord-311035-s3tkbh9r 113 19 mutations mutation NNS cord-311035-s3tkbh9r 113 20 on on IN cord-311035-s3tkbh9r 113 21 RBD RBD NNP cord-311035-s3tkbh9r 113 22 surface surface NN cord-311035-s3tkbh9r 113 23 display display NN cord-311035-s3tkbh9r 113 24 were be VBD cord-311035-s3tkbh9r 113 25 also also RB cord-311035-s3tkbh9r 113 26 assessed assess VBN cord-311035-s3tkbh9r 113 27 in in IN cord-311035-s3tkbh9r 113 28 a a DT cord-311035-s3tkbh9r 113 29 standalone standalone JJ cord-311035-s3tkbh9r 113 30 FACS FACS NNP cord-311035-s3tkbh9r 113 31 selection selection NN cord-311035-s3tkbh9r 113 32 . . . cord-311035-s3tkbh9r 114 1 Quality quality NN cord-311035-s3tkbh9r 114 2 control control NN cord-311035-s3tkbh9r 114 3 pathways pathway NNS cord-311035-s3tkbh9r 114 4 for for IN cord-311035-s3tkbh9r 114 5 protein protein NN cord-311035-s3tkbh9r 114 6 secretion secretion NN cord-311035-s3tkbh9r 114 7 in in IN cord-311035-s3tkbh9r 114 8 yeast yeast NN cord-311035-s3tkbh9r 114 9 can can MD cord-311035-s3tkbh9r 114 10 be be VB cord-311035-s3tkbh9r 114 11 forgiving forgiving JJ cord-311035-s3tkbh9r 114 12 of of IN cord-311035-s3tkbh9r 114 13 misfolded misfolded JJ cord-311035-s3tkbh9r 114 14 protein protein NN cord-311035-s3tkbh9r 114 15 sequences sequence NNS cord-311035-s3tkbh9r 114 16 [ [ -LRB- cord-311035-s3tkbh9r 114 17 16 16 CD cord-311035-s3tkbh9r 114 18 ] ] -RRB- cord-311035-s3tkbh9r 114 19 and and CC cord-311035-s3tkbh9r 114 20 there there EX cord-311035-s3tkbh9r 114 21 are be VBP cord-311035-s3tkbh9r 114 22 residues residue NNS cord-311035-s3tkbh9r 114 23 of of IN cord-311035-s3tkbh9r 114 24 the the DT cord-311035-s3tkbh9r 114 25 RBD RBD NNP cord-311035-s3tkbh9r 114 26 that that WDT cord-311035-s3tkbh9r 114 27 would would MD cord-311035-s3tkbh9r 114 28 ordinarily ordinarily RB cord-311035-s3tkbh9r 114 29 be be VB cord-311035-s3tkbh9r 114 30 buried bury VBN cord-311035-s3tkbh9r 114 31 in in IN cord-311035-s3tkbh9r 114 32 the the DT cord-311035-s3tkbh9r 114 33 context context NN cord-311035-s3tkbh9r 114 34 of of IN cord-311035-s3tkbh9r 114 35 the the DT cord-311035-s3tkbh9r 114 36 full full JJ cord-311035-s3tkbh9r 114 37 S S NNP cord-311035-s3tkbh9r 114 38 protein protein NN cord-311035-s3tkbh9r 114 39 ; ; : cord-311035-s3tkbh9r 114 40 it -PRON- PRP cord-311035-s3tkbh9r 114 41 therefore therefore RB cord-311035-s3tkbh9r 114 42 remains remain VBZ cord-311035-s3tkbh9r 114 43 to to TO cord-311035-s3tkbh9r 114 44 be be VB cord-311035-s3tkbh9r 114 45 seen see VBN cord-311035-s3tkbh9r 114 46 how how WRB cord-311035-s3tkbh9r 114 47 closely closely RB cord-311035-s3tkbh9r 114 48 the the DT cord-311035-s3tkbh9r 114 49 yeast yeast NN cord-311035-s3tkbh9r 114 50 display display NN cord-311035-s3tkbh9r 114 51 data datum NNS cord-311035-s3tkbh9r 114 52 will will MD cord-311035-s3tkbh9r 114 53 correlate correlate VB cord-311035-s3tkbh9r 114 54 with with IN cord-311035-s3tkbh9r 114 55 equivalent equivalent JJ cord-311035-s3tkbh9r 114 56 experiments experiment NNS cord-311035-s3tkbh9r 114 57 in in IN cord-311035-s3tkbh9r 114 58 more more RBR cord-311035-s3tkbh9r 114 59 physiologically physiologically RB cord-311035-s3tkbh9r 114 60 relevant relevant JJ cord-311035-s3tkbh9r 114 61 expression expression NN cord-311035-s3tkbh9r 114 62 systems system NNS cord-311035-s3tkbh9r 114 63 . . . cord-311035-s3tkbh9r 115 1 Nonetheless nonetheless RB cord-311035-s3tkbh9r 115 2 , , , cord-311035-s3tkbh9r 115 3 the the DT cord-311035-s3tkbh9r 115 4 predicted predict VBN cord-311035-s3tkbh9r 115 5 effects effect NNS cord-311035-s3tkbh9r 115 6 by by IN cord-311035-s3tkbh9r 115 7 yeast yeast NN cord-311035-s3tkbh9r 115 8 display display NN cord-311035-s3tkbh9r 115 9 of of IN cord-311035-s3tkbh9r 115 10 some some DT cord-311035-s3tkbh9r 115 11 mutations mutation NNS cord-311035-s3tkbh9r 115 12 were be VBD cord-311035-s3tkbh9r 115 13 validated validate VBN cord-311035-s3tkbh9r 115 14 using use VBG cord-311035-s3tkbh9r 115 15 full full JJ cord-311035-s3tkbh9r 115 16 length length NN cord-311035-s3tkbh9r 115 17 S S NNP cord-311035-s3tkbh9r 115 18 expressed express VBN cord-311035-s3tkbh9r 115 19 in in IN cord-311035-s3tkbh9r 115 20 human human JJ cord-311035-s3tkbh9r 115 21 cells cell NNS cord-311035-s3tkbh9r 115 22 and and CC cord-311035-s3tkbh9r 115 23 packaged package VBN cord-311035-s3tkbh9r 115 24 in in IN cord-311035-s3tkbh9r 115 25 pseudovirus pseudovirus NNP cord-311035-s3tkbh9r 115 26 [ [ -LRB- cord-311035-s3tkbh9r 115 27 14 14 CD cord-311035-s3tkbh9r 115 28 ] ] -RRB- cord-311035-s3tkbh9r 115 29 . . . cord-311035-s3tkbh9r 116 1 The the DT cord-311035-s3tkbh9r 116 2 library library NN cord-311035-s3tkbh9r 116 3 encoding encode VBG cord-311035-s3tkbh9r 116 4 nearly nearly RB cord-311035-s3tkbh9r 116 5 4,000 4,000 CD cord-311035-s3tkbh9r 116 6 single single JJ cord-311035-s3tkbh9r 116 7 amino amino NN cord-311035-s3tkbh9r 116 8 acid acid NN cord-311035-s3tkbh9r 116 9 substitutions substitution NNS cord-311035-s3tkbh9r 116 10 in in IN cord-311035-s3tkbh9r 116 11 the the DT cord-311035-s3tkbh9r 116 12 SARS SARS NNP cord-311035-s3tkbh9r 116 13 - - HYPH cord-311035-s3tkbh9r 116 14 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 116 15 RBD RBD NNP cord-311035-s3tkbh9r 116 16 was be VBD cord-311035-s3tkbh9r 116 17 PacBio pacbio NN cord-311035-s3tkbh9r 116 18 sequenced sequence VBN cord-311035-s3tkbh9r 116 19 , , , cord-311035-s3tkbh9r 116 20 providing provide VBG cord-311035-s3tkbh9r 116 21 long long JJ cord-311035-s3tkbh9r 116 22 reads read NNS cord-311035-s3tkbh9r 116 23 that that WDT cord-311035-s3tkbh9r 116 24 match match VBP cord-311035-s3tkbh9r 116 25 untranslated untranslated JJ cord-311035-s3tkbh9r 116 26 nucleotide nucleotide NN cord-311035-s3tkbh9r 116 27 barcodes barcode NNS cord-311035-s3tkbh9r 116 28 to to IN cord-311035-s3tkbh9r 116 29 a a DT cord-311035-s3tkbh9r 116 30 specific specific JJ cord-311035-s3tkbh9r 116 31 protein protein NN cord-311035-s3tkbh9r 116 32 variant variant NN cord-311035-s3tkbh9r 116 33 . . . cord-311035-s3tkbh9r 117 1 Following follow VBG cord-311035-s3tkbh9r 117 2 FACS FACS NNP cord-311035-s3tkbh9r 117 3 - - HYPH cord-311035-s3tkbh9r 117 4 based base VBN cord-311035-s3tkbh9r 117 5 selection selection NN cord-311035-s3tkbh9r 117 6 , , , cord-311035-s3tkbh9r 117 7 only only RB cord-311035-s3tkbh9r 117 8 the the DT cord-311035-s3tkbh9r 117 9 barcodes barcode NNS cord-311035-s3tkbh9r 117 10 are be VBP cord-311035-s3tkbh9r 117 11 read read VBN cord-311035-s3tkbh9r 117 12 to to TO cord-311035-s3tkbh9r 117 13 determine determine VB cord-311035-s3tkbh9r 117 14 how how WRB cord-311035-s3tkbh9r 117 15 favorable favorable JJ cord-311035-s3tkbh9r 117 16 sequence sequence NN cord-311035-s3tkbh9r 117 17 variants variant NNS cord-311035-s3tkbh9r 117 18 are be VBP cord-311035-s3tkbh9r 117 19 enriched enrich VBN cord-311035-s3tkbh9r 117 20 or or CC cord-311035-s3tkbh9r 117 21 deleterious deleterious JJ cord-311035-s3tkbh9r 117 22 sequence sequence NN cord-311035-s3tkbh9r 117 23 variants variant NNS cord-311035-s3tkbh9r 117 24 are be VBP cord-311035-s3tkbh9r 117 25 depleted deplete VBN cord-311035-s3tkbh9r 117 26 . . . cord-311035-s3tkbh9r 118 1 This this DT cord-311035-s3tkbh9r 118 2 resolves resolve VBZ cord-311035-s3tkbh9r 118 3 issues issue NNS cord-311035-s3tkbh9r 118 4 with with IN cord-311035-s3tkbh9r 118 5 Illumina Illumina NNP cord-311035-s3tkbh9r 118 6 sequencing sequencing NN cord-311035-s3tkbh9r 118 7 failing fail VBG cord-311035-s3tkbh9r 118 8 to to TO cord-311035-s3tkbh9r 118 9 cover cover VB cord-311035-s3tkbh9r 118 10 the the DT cord-311035-s3tkbh9r 118 11 full full JJ cord-311035-s3tkbh9r 118 12 cDNA cdna NN cord-311035-s3tkbh9r 118 13 length length NN cord-311035-s3tkbh9r 118 14 , , , cord-311035-s3tkbh9r 118 15 and and CC cord-311035-s3tkbh9r 118 16 because because IN cord-311035-s3tkbh9r 118 17 multiple multiple JJ cord-311035-s3tkbh9r 118 18 barcodes barcode NNS cord-311035-s3tkbh9r 118 19 are be VBP cord-311035-s3tkbh9r 118 20 associated associate VBN cord-311035-s3tkbh9r 118 21 with with IN cord-311035-s3tkbh9r 118 22 any any DT cord-311035-s3tkbh9r 118 23 given give VBN cord-311035-s3tkbh9r 118 24 protein protein NN cord-311035-s3tkbh9r 118 25 variant variant NN cord-311035-s3tkbh9r 118 26 , , , cord-311035-s3tkbh9r 118 27 there there EX cord-311035-s3tkbh9r 118 28 are be VBP cord-311035-s3tkbh9r 118 29 additional additional JJ cord-311035-s3tkbh9r 118 30 internal internal JJ cord-311035-s3tkbh9r 118 31 checks check NNS cord-311035-s3tkbh9r 118 32 for for IN cord-311035-s3tkbh9r 118 33 data data NN cord-311035-s3tkbh9r 118 34 quality quality NN cord-311035-s3tkbh9r 118 35 and and CC cord-311035-s3tkbh9r 118 36 consistency consistency NN cord-311035-s3tkbh9r 118 37 . . . cord-311035-s3tkbh9r 119 1 Despite despite IN cord-311035-s3tkbh9r 119 2 the the DT cord-311035-s3tkbh9r 119 3 limitations limitation NNS cord-311035-s3tkbh9r 119 4 of of IN cord-311035-s3tkbh9r 119 5 a a DT cord-311035-s3tkbh9r 119 6 yeast yeast NN cord-311035-s3tkbh9r 119 7 display display NN cord-311035-s3tkbh9r 119 8 platform platform NN cord-311035-s3tkbh9r 119 9 , , , cord-311035-s3tkbh9r 119 10 the the DT cord-311035-s3tkbh9r 119 11 deep deep JJ cord-311035-s3tkbh9r 119 12 mutational mutational JJ cord-311035-s3tkbh9r 119 13 scan scan NN cord-311035-s3tkbh9r 119 14 of of IN cord-311035-s3tkbh9r 119 15 the the DT cord-311035-s3tkbh9r 119 16 isolated isolate VBN cord-311035-s3tkbh9r 119 17 RBD RBD NNP cord-311035-s3tkbh9r 119 18 provides provide VBZ cord-311035-s3tkbh9r 119 19 a a DT cord-311035-s3tkbh9r 119 20 high high JJ cord-311035-s3tkbh9r 119 21 quality quality NN cord-311035-s3tkbh9r 119 22 and and CC cord-311035-s3tkbh9r 119 23 useful useful JJ cord-311035-s3tkbh9r 119 24 data datum NNS cord-311035-s3tkbh9r 119 25 set set VBN cord-311035-s3tkbh9r 119 26 from from IN cord-311035-s3tkbh9r 119 27 which which WDT cord-311035-s3tkbh9r 119 28 several several JJ cord-311035-s3tkbh9r 119 29 important important JJ cord-311035-s3tkbh9r 119 30 conclusions conclusion NNS cord-311035-s3tkbh9r 119 31 were be VBD cord-311035-s3tkbh9r 119 32 drawn draw VBN cord-311035-s3tkbh9r 119 33 . . . cord-311035-s3tkbh9r 120 1 First first RB cord-311035-s3tkbh9r 120 2 , , , cord-311035-s3tkbh9r 120 3 the the DT cord-311035-s3tkbh9r 120 4 ACE2 ACE2 NNP cord-311035-s3tkbh9r 120 5 binding binding NN cord-311035-s3tkbh9r 120 6 surface surface NN cord-311035-s3tkbh9r 120 7 of of IN cord-311035-s3tkbh9r 120 8 SARS SARS NNP cord-311035-s3tkbh9r 120 9 - - HYPH cord-311035-s3tkbh9r 120 10 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 120 11 RBD RBD NNP cord-311035-s3tkbh9r 120 12 tolerates tolerate VBZ cord-311035-s3tkbh9r 120 13 surprisingly surprisingly RB cord-311035-s3tkbh9r 120 14 high high JJ cord-311035-s3tkbh9r 120 15 sequence sequence NN cord-311035-s3tkbh9r 120 16 diversity diversity NN cord-311035-s3tkbh9r 120 17 , , , cord-311035-s3tkbh9r 120 18 even even RB cord-311035-s3tkbh9r 120 19 though though IN cord-311035-s3tkbh9r 120 20 it -PRON- PRP cord-311035-s3tkbh9r 120 21 is be VBZ cord-311035-s3tkbh9r 120 22 a a DT cord-311035-s3tkbh9r 120 23 critical critical JJ cord-311035-s3tkbh9r 120 24 site site NN cord-311035-s3tkbh9r 120 25 for for IN cord-311035-s3tkbh9r 120 26 function function NN cord-311035-s3tkbh9r 120 27 [ [ -LRB- cord-311035-s3tkbh9r 120 28 14 14 CD cord-311035-s3tkbh9r 120 29 ] ] -RRB- cord-311035-s3tkbh9r 120 30 . . . cord-311035-s3tkbh9r 121 1 High high JJ cord-311035-s3tkbh9r 121 2 diversity diversity NN cord-311035-s3tkbh9r 121 3 is be VBZ cord-311035-s3tkbh9r 121 4 also also RB cord-311035-s3tkbh9r 121 5 seen see VBN cord-311035-s3tkbh9r 121 6 in in IN cord-311035-s3tkbh9r 121 7 the the DT cord-311035-s3tkbh9r 121 8 ACE2-binding ace2-binde VBG cord-311035-s3tkbh9r 121 9 sites site NNS cord-311035-s3tkbh9r 121 10 of of IN cord-311035-s3tkbh9r 121 11 S S NNP cord-311035-s3tkbh9r 121 12 proteins protein NNS cord-311035-s3tkbh9r 121 13 from from IN cord-311035-s3tkbh9r 121 14 SARS SARS NNP cord-311035-s3tkbh9r 121 15 - - HYPH cord-311035-s3tkbh9r 121 16 related relate VBN cord-311035-s3tkbh9r 121 17 bat bat NN cord-311035-s3tkbh9r 121 18 coronaviruses coronaviruse NNS cord-311035-s3tkbh9r 121 19 , , , cord-311035-s3tkbh9r 121 20 but but CC cord-311035-s3tkbh9r 121 21 this this DT cord-311035-s3tkbh9r 121 22 matches match VBZ cord-311035-s3tkbh9r 121 23 corresponding correspond VBG cord-311035-s3tkbh9r 121 24 diversity diversity NN cord-311035-s3tkbh9r 121 25 in in IN cord-311035-s3tkbh9r 121 26 ACE2 ACE2 NNP cord-311035-s3tkbh9r 121 27 from from IN cord-311035-s3tkbh9r 121 28 ecologically ecologically RB cord-311035-s3tkbh9r 121 29 diverse diverse JJ cord-311035-s3tkbh9r 121 30 bat bat NN cord-311035-s3tkbh9r 121 31 species specie NNS cord-311035-s3tkbh9r 121 32 [ [ -LRB- cord-311035-s3tkbh9r 121 33 56 56 CD cord-311035-s3tkbh9r 121 34 ] ] -RRB- cord-311035-s3tkbh9r 121 35 and and CC cord-311035-s3tkbh9r 121 36 does do VBZ cord-311035-s3tkbh9r 121 37 not not RB cord-311035-s3tkbh9r 121 38 necessarily necessarily RB cord-311035-s3tkbh9r 121 39 mean mean VB cord-311035-s3tkbh9r 121 40 that that IN cord-311035-s3tkbh9r 121 41 the the DT cord-311035-s3tkbh9r 121 42 RBD RBD NNP cord-311035-s3tkbh9r 121 43 tolerates tolerate VBZ cord-311035-s3tkbh9r 121 44 mutations mutation NNS cord-311035-s3tkbh9r 121 45 for for IN cord-311035-s3tkbh9r 121 46 binding bind VBG cord-311035-s3tkbh9r 121 47 ACE2 ACE2 NNP cord-311035-s3tkbh9r 121 48 from from IN cord-311035-s3tkbh9r 121 49 a a DT cord-311035-s3tkbh9r 121 50 single single JJ cord-311035-s3tkbh9r 121 51 species specie NNS cord-311035-s3tkbh9r 121 52 . . . cord-311035-s3tkbh9r 122 1 The the DT cord-311035-s3tkbh9r 122 2 deep deep JJ cord-311035-s3tkbh9r 122 3 mutational mutational JJ cord-311035-s3tkbh9r 122 4 scan scan NN cord-311035-s3tkbh9r 122 5 addresses address NNS cord-311035-s3tkbh9r 122 6 this this DT cord-311035-s3tkbh9r 122 7 uncertainty uncertainty NN cord-311035-s3tkbh9r 122 8 and and CC cord-311035-s3tkbh9r 122 9 is be VBZ cord-311035-s3tkbh9r 122 10 further further RB cord-311035-s3tkbh9r 122 11 supported support VBN cord-311035-s3tkbh9r 122 12 by by IN cord-311035-s3tkbh9r 122 13 evidence evidence NN cord-311035-s3tkbh9r 122 14 showing show VBG cord-311035-s3tkbh9r 122 15 that that IN cord-311035-s3tkbh9r 122 16 diverse diverse JJ cord-311035-s3tkbh9r 122 17 RBD rbd NN cord-311035-s3tkbh9r 122 18 sequences sequence NNS cord-311035-s3tkbh9r 122 19 from from IN cord-311035-s3tkbh9r 122 20 bat bat NN cord-311035-s3tkbh9r 122 21 coronaviruses coronaviruse NNS cord-311035-s3tkbh9r 122 22 are be VBP cord-311035-s3tkbh9r 122 23 all all DT cord-311035-s3tkbh9r 122 24 competent competent JJ cord-311035-s3tkbh9r 122 25 for for IN cord-311035-s3tkbh9r 122 26 binding bind VBG cord-311035-s3tkbh9r 122 27 human human JJ cord-311035-s3tkbh9r 122 28 ACE2 ACE2 NNP cord-311035-s3tkbh9r 122 29 with with IN cord-311035-s3tkbh9r 122 30 varying vary VBG cord-311035-s3tkbh9r 122 31 affinities affinity NNS cord-311035-s3tkbh9r 122 32 [ [ -LRB- cord-311035-s3tkbh9r 122 33 38 38 CD cord-311035-s3tkbh9r 122 34 ] ] -RRB- cord-311035-s3tkbh9r 122 35 . . . cord-311035-s3tkbh9r 123 1 Second second RB cord-311035-s3tkbh9r 123 2 , , , cord-311035-s3tkbh9r 123 3 mutations mutation NNS cord-311035-s3tkbh9r 123 4 were be VBD cord-311035-s3tkbh9r 123 5 found find VBN cord-311035-s3tkbh9r 123 6 in in IN cord-311035-s3tkbh9r 123 7 the the DT cord-311035-s3tkbh9r 123 8 RBD RBD NNP cord-311035-s3tkbh9r 123 9 that that WDT cord-311035-s3tkbh9r 123 10 enhance enhance VBP cord-311035-s3tkbh9r 123 11 binding binding NN cord-311035-s3tkbh9r 123 12 to to IN cord-311035-s3tkbh9r 123 13 ACE2 ACE2 NNP cord-311035-s3tkbh9r 123 14 , , , cord-311035-s3tkbh9r 123 15 yet yet CC cord-311035-s3tkbh9r 123 16 there there EX cord-311035-s3tkbh9r 123 17 does do VBZ cord-311035-s3tkbh9r 123 18 not not RB cord-311035-s3tkbh9r 123 19 appear appear VB cord-311035-s3tkbh9r 123 20 to to TO cord-311035-s3tkbh9r 123 21 be be VB cord-311035-s3tkbh9r 123 22 positive positive JJ cord-311035-s3tkbh9r 123 23 selective selective JJ cord-311035-s3tkbh9r 123 24 pressure pressure NN cord-311035-s3tkbh9r 123 25 for for IN cord-311035-s3tkbh9r 123 26 these these DT cord-311035-s3tkbh9r 123 27 variants variant NNS cord-311035-s3tkbh9r 123 28 in in IN cord-311035-s3tkbh9r 123 29 the the DT cord-311035-s3tkbh9r 123 30 human human JJ cord-311035-s3tkbh9r 123 31 population population NN cord-311035-s3tkbh9r 123 32 [ [ -LRB- cord-311035-s3tkbh9r 123 33 14 14 CD cord-311035-s3tkbh9r 123 34 ] ] -RRB- cord-311035-s3tkbh9r 123 35 . . . cord-311035-s3tkbh9r 124 1 SARS SARS NNP cord-311035-s3tkbh9r 124 2 - - HYPH cord-311035-s3tkbh9r 124 3 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 124 4 affinity affinity NN cord-311035-s3tkbh9r 124 5 for for IN cord-311035-s3tkbh9r 124 6 ACE2 ACE2 NNP cord-311035-s3tkbh9r 124 7 is be VBZ cord-311035-s3tkbh9r 124 8 therefore therefore RB cord-311035-s3tkbh9r 124 9 ' ' `` cord-311035-s3tkbh9r 124 10 good good JJ cord-311035-s3tkbh9r 124 11 enough enough RB cord-311035-s3tkbh9r 124 12 , , , cord-311035-s3tkbh9r 124 13 ' ' '' cord-311035-s3tkbh9r 124 14 with with IN cord-311035-s3tkbh9r 124 15 no no DT cord-311035-s3tkbh9r 124 16 additional additional JJ cord-311035-s3tkbh9r 124 17 fitness fitness NN cord-311035-s3tkbh9r 124 18 benefit benefit NN cord-311035-s3tkbh9r 124 19 for for IN cord-311035-s3tkbh9r 124 20 higher high JJR cord-311035-s3tkbh9r 124 21 affinity affinity NN cord-311035-s3tkbh9r 124 22 . . . cord-311035-s3tkbh9r 125 1 It -PRON- PRP cord-311035-s3tkbh9r 125 2 is be VBZ cord-311035-s3tkbh9r 125 3 worth worth JJ cord-311035-s3tkbh9r 125 4 noting note VBG cord-311035-s3tkbh9r 125 5 that that IN cord-311035-s3tkbh9r 125 6 classical classical JJ cord-311035-s3tkbh9r 125 7 SARS SARS NNP cord-311035-s3tkbh9r 125 8 - - HYPH cord-311035-s3tkbh9r 125 9 CoV-1 CoV-1 NNP cord-311035-s3tkbh9r 125 10 is be VBZ cord-311035-s3tkbh9r 125 11 also also RB cord-311035-s3tkbh9r 125 12 a a DT cord-311035-s3tkbh9r 125 13 highly highly RB cord-311035-s3tkbh9r 125 14 infectious infectious JJ cord-311035-s3tkbh9r 125 15 and and CC cord-311035-s3tkbh9r 125 16 virulent virulent JJ cord-311035-s3tkbh9r 125 17 pathogen pathogen NN cord-311035-s3tkbh9r 125 18 , , , cord-311035-s3tkbh9r 125 19 despite despite IN cord-311035-s3tkbh9r 125 20 having have VBG cord-311035-s3tkbh9r 125 21 weaker weak JJR cord-311035-s3tkbh9r 125 22 ACE2 ACE2 NNP cord-311035-s3tkbh9r 125 23 affinity affinity NN cord-311035-s3tkbh9r 125 24 [ [ -LRB- cord-311035-s3tkbh9r 125 25 36 36 CD cord-311035-s3tkbh9r 125 26 , , , cord-311035-s3tkbh9r 125 27 57 57 CD cord-311035-s3tkbh9r 125 28 ] ] -RRB- cord-311035-s3tkbh9r 125 29 . . . cord-311035-s3tkbh9r 126 1 The the DT cord-311035-s3tkbh9r 126 2 rapid rapid JJ cord-311035-s3tkbh9r 126 3 spread spread NN cord-311035-s3tkbh9r 126 4 of of IN cord-311035-s3tkbh9r 126 5 SARS SARS NNP cord-311035-s3tkbh9r 126 6 - - HYPH cord-311035-s3tkbh9r 126 7 CoV CoV NNP cord-311035-s3tkbh9r 126 8 -2 -2 XX cord-311035-s3tkbh9r 126 9 probably probably RB cord-311035-s3tkbh9r 126 10 has have VBZ cord-311035-s3tkbh9r 126 11 more more JJR cord-311035-s3tkbh9r 126 12 to to TO cord-311035-s3tkbh9r 126 13 do do VB cord-311035-s3tkbh9r 126 14 with with IN cord-311035-s3tkbh9r 126 15 asymptomatic asymptomatic JJ cord-311035-s3tkbh9r 126 16 and and CC cord-311035-s3tkbh9r 126 17 presymptomatic presymptomatic JJ cord-311035-s3tkbh9r 126 18 transmission transmission NN cord-311035-s3tkbh9r 126 19 than than IN cord-311035-s3tkbh9r 126 20 enhanced enhance VBN cord-311035-s3tkbh9r 126 21 receptor receptor NN cord-311035-s3tkbh9r 126 22 binding binding NN cord-311035-s3tkbh9r 126 23 . . . cord-311035-s3tkbh9r 127 1 Third third RB cord-311035-s3tkbh9r 127 2 , , , cord-311035-s3tkbh9r 127 3 mutations mutation NNS cord-311035-s3tkbh9r 127 4 were be VBD cord-311035-s3tkbh9r 127 5 found find VBN cord-311035-s3tkbh9r 127 6 within within IN cord-311035-s3tkbh9r 127 7 the the DT cord-311035-s3tkbh9r 127 8 epitopes epitope NNS cord-311035-s3tkbh9r 127 9 for for IN cord-311035-s3tkbh9r 127 10 monoclonal monoclonal JJ cord-311035-s3tkbh9r 127 11 antibodies antibody NNS cord-311035-s3tkbh9r 127 12 but but CC cord-311035-s3tkbh9r 127 13 maintain maintain VBP cord-311035-s3tkbh9r 127 14 high high JJ cord-311035-s3tkbh9r 127 15 ACE2 ACE2 NNP cord-311035-s3tkbh9r 127 16 binding binding NN cord-311035-s3tkbh9r 127 17 , , , cord-311035-s3tkbh9r 127 18 and and CC cord-311035-s3tkbh9r 127 19 it -PRON- PRP cord-311035-s3tkbh9r 127 20 is be VBZ cord-311035-s3tkbh9r 127 21 likely likely JJ cord-311035-s3tkbh9r 127 22 that that IN cord-311035-s3tkbh9r 127 23 SARS SARS NNP cord-311035-s3tkbh9r 127 24 - - HYPH cord-311035-s3tkbh9r 127 25 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 127 26 can can MD cord-311035-s3tkbh9r 127 27 easily easily RB cord-311035-s3tkbh9r 127 28 mutate mutate VB cord-311035-s3tkbh9r 127 29 to to TO cord-311035-s3tkbh9r 127 30 escape escape VB cord-311035-s3tkbh9r 127 31 neutralization neutralization NN cord-311035-s3tkbh9r 127 32 without without IN cord-311035-s3tkbh9r 127 33 losing lose VBG cord-311035-s3tkbh9r 127 34 infectivity infectivity NN cord-311035-s3tkbh9r 127 35 [ [ -LRB- cord-311035-s3tkbh9r 127 36 14 14 CD cord-311035-s3tkbh9r 127 37 ] ] -RRB- cord-311035-s3tkbh9r 127 38 . . . cord-311035-s3tkbh9r 128 1 This this DT cord-311035-s3tkbh9r 128 2 agrees agree VBZ cord-311035-s3tkbh9r 128 3 with with IN cord-311035-s3tkbh9r 128 4 selection selection NN cord-311035-s3tkbh9r 128 5 experiments experiment NNS cord-311035-s3tkbh9r 128 6 of of IN cord-311035-s3tkbh9r 128 7 pseudovirus pseudovirus NNP cord-311035-s3tkbh9r 128 8 expressing express VBG cord-311035-s3tkbh9r 128 9 SARS SARS NNP cord-311035-s3tkbh9r 128 10 - - HYPH cord-311035-s3tkbh9r 128 11 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 128 12 S S NNP cord-311035-s3tkbh9r 128 13 variants variant NNS cord-311035-s3tkbh9r 128 14 , , , cord-311035-s3tkbh9r 128 15 in in IN cord-311035-s3tkbh9r 128 16 which which WDT cord-311035-s3tkbh9r 128 17 escape escape NN cord-311035-s3tkbh9r 128 18 mutants mutant NNS cord-311035-s3tkbh9r 128 19 in in IN cord-311035-s3tkbh9r 128 20 the the DT cord-311035-s3tkbh9r 128 21 viral viral JJ cord-311035-s3tkbh9r 128 22 spike spike NN cord-311035-s3tkbh9r 128 23 rapidly rapidly RB cord-311035-s3tkbh9r 128 24 emerge emerge VBP cord-311035-s3tkbh9r 128 25 to to IN cord-311035-s3tkbh9r 128 26 neutralizing neutralize VBG cord-311035-s3tkbh9r 128 27 antibodies antibody NNS cord-311035-s3tkbh9r 128 28 in in IN cord-311035-s3tkbh9r 128 29 a a DT cord-311035-s3tkbh9r 128 30 single single JJ cord-311035-s3tkbh9r 128 31 passage passage NN cord-311035-s3tkbh9r 128 32 [ [ -LRB- cord-311035-s3tkbh9r 128 33 43 43 CD cord-311035-s3tkbh9r 128 34 ] ] -RRB- cord-311035-s3tkbh9r 128 35 . . . cord-311035-s3tkbh9r 129 1 This this DT cord-311035-s3tkbh9r 129 2 has have VBZ cord-311035-s3tkbh9r 129 3 profound profound JJ cord-311035-s3tkbh9r 129 4 implications implication NNS cord-311035-s3tkbh9r 129 5 for for IN cord-311035-s3tkbh9r 129 6 antibody antibody NN cord-311035-s3tkbh9r 129 7 therapy therapy NN cord-311035-s3tkbh9r 129 8 , , , cord-311035-s3tkbh9r 129 9 where where WRB cord-311035-s3tkbh9r 129 10 the the DT cord-311035-s3tkbh9r 129 11 standard standard NN cord-311035-s3tkbh9r 129 12 has have VBZ cord-311035-s3tkbh9r 129 13 become become VBN cord-311035-s3tkbh9r 129 14 combinations combination NNS cord-311035-s3tkbh9r 129 15 of of IN cord-311035-s3tkbh9r 129 16 noncompeting noncompeting NN cord-311035-s3tkbh9r 129 17 monoclonals monoclonal NNS cord-311035-s3tkbh9r 129 18 in in IN cord-311035-s3tkbh9r 129 19 a a DT cord-311035-s3tkbh9r 129 20 cocktail cocktail NN cord-311035-s3tkbh9r 129 21 to to TO cord-311035-s3tkbh9r 129 22 prevent prevent VB cord-311035-s3tkbh9r 129 23 rapid rapid JJ cord-311035-s3tkbh9r 129 24 resistance resistance NN cord-311035-s3tkbh9r 129 25 . . . cord-311035-s3tkbh9r 130 1 It -PRON- PRP cord-311035-s3tkbh9r 130 2 is be VBZ cord-311035-s3tkbh9r 130 3 currently currently RB cord-311035-s3tkbh9r 130 4 unknown unknown JJ cord-311035-s3tkbh9r 130 5 whether whether IN cord-311035-s3tkbh9r 130 6 an an DT cord-311035-s3tkbh9r 130 7 engineered engineer VBN cord-311035-s3tkbh9r 130 8 soluble soluble JJ cord-311035-s3tkbh9r 130 9 decoy decoy NN cord-311035-s3tkbh9r 130 10 receptor receptor NN cord-311035-s3tkbh9r 130 11 , , , cord-311035-s3tkbh9r 130 12 such such JJ cord-311035-s3tkbh9r 130 13 as as IN cord-311035-s3tkbh9r 130 14 sACE2 sACE2 NNS cord-311035-s3tkbh9r 130 15 2 2 CD cord-311035-s3tkbh9r 130 16 .v2.4 .v2.4 NFP cord-311035-s3tkbh9r 130 17 , , , cord-311035-s3tkbh9r 130 18 will will MD cord-311035-s3tkbh9r 130 19 similarly similarly RB cord-311035-s3tkbh9r 130 20 be be VB cord-311035-s3tkbh9r 130 21 susceptible susceptible JJ cord-311035-s3tkbh9r 130 22 to to IN cord-311035-s3tkbh9r 130 23 the the DT cord-311035-s3tkbh9r 130 24 emergence emergence NN cord-311035-s3tkbh9r 130 25 of of IN cord-311035-s3tkbh9r 130 26 viral viral JJ cord-311035-s3tkbh9r 130 27 spike spike NN cord-311035-s3tkbh9r 130 28 variants variant NNS cord-311035-s3tkbh9r 130 29 that that WDT cord-311035-s3tkbh9r 130 30 can can MD cord-311035-s3tkbh9r 130 31 discriminate discriminate VB cord-311035-s3tkbh9r 130 32 between between IN cord-311035-s3tkbh9r 130 33 the the DT cord-311035-s3tkbh9r 130 34 engineered engineer VBN cord-311035-s3tkbh9r 130 35 decoy decoy NN cord-311035-s3tkbh9r 130 36 and and CC cord-311035-s3tkbh9r 130 37 the the DT cord-311035-s3tkbh9r 130 38 native native JJ cord-311035-s3tkbh9r 130 39 receptor receptor NN cord-311035-s3tkbh9r 130 40 . . . cord-311035-s3tkbh9r 131 1 We -PRON- PRP cord-311035-s3tkbh9r 131 2 hypothesize hypothesize VBP cord-311035-s3tkbh9r 131 3 that that IN cord-311035-s3tkbh9r 131 4 engineered engineer VBN cord-311035-s3tkbh9r 131 5 decoys decoy NNS cord-311035-s3tkbh9r 131 6 will will MD cord-311035-s3tkbh9r 131 7 be be VB cord-311035-s3tkbh9r 131 8 broadly broadly RB cord-311035-s3tkbh9r 131 9 active active JJ cord-311035-s3tkbh9r 131 10 against against IN cord-311035-s3tkbh9r 131 11 SARS SARS NNP cord-311035-s3tkbh9r 131 12 - - HYPH cord-311035-s3tkbh9r 131 13 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 131 14 variants variant NNS cord-311035-s3tkbh9r 131 15 and and CC cord-311035-s3tkbh9r 131 16 this this DT cord-311035-s3tkbh9r 131 17 remains remain VBZ cord-311035-s3tkbh9r 131 18 an an DT cord-311035-s3tkbh9r 131 19 active active JJ cord-311035-s3tkbh9r 131 20 area area NN cord-311035-s3tkbh9r 131 21 of of IN cord-311035-s3tkbh9r 131 22 investigation investigation NN cord-311035-s3tkbh9r 131 23 . . . cord-311035-s3tkbh9r 132 1 http://orcid.org/0000-0002-0028-490X http://orcid.org/0000-0002-0028-490X NNP cord-311035-s3tkbh9r 132 2 Papers Papers NNPS cord-311035-s3tkbh9r 132 3 of of IN cord-311035-s3tkbh9r 132 4 special special JJ cord-311035-s3tkbh9r 132 5 note note NN cord-311035-s3tkbh9r 132 6 have have VBP cord-311035-s3tkbh9r 132 7 been be VBN cord-311035-s3tkbh9r 132 8 highlighted highlight VBN cord-311035-s3tkbh9r 132 9 as as IN cord-311035-s3tkbh9r 132 10 either either DT cord-311035-s3tkbh9r 132 11 of of IN cord-311035-s3tkbh9r 132 12 interest interest NN cord-311035-s3tkbh9r 132 13 ( ( -LRB- cord-311035-s3tkbh9r 132 14 • • NNP cord-311035-s3tkbh9r 132 15 ) ) -RRB- cord-311035-s3tkbh9r 132 16 or or CC cord-311035-s3tkbh9r 132 17 of of IN cord-311035-s3tkbh9r 132 18 considerable considerable JJ cord-311035-s3tkbh9r 132 19 interest interest NN cord-311035-s3tkbh9r 132 20 Deep deep JJ cord-311035-s3tkbh9r 132 21 mutational mutational JJ cord-311035-s3tkbh9r 132 22 scanning scanning NN cord-311035-s3tkbh9r 132 23 : : : cord-311035-s3tkbh9r 132 24 a a DT cord-311035-s3tkbh9r 132 25 new new JJ cord-311035-s3tkbh9r 132 26 style style NN cord-311035-s3tkbh9r 132 27 of of IN cord-311035-s3tkbh9r 132 28 protein protein NN cord-311035-s3tkbh9r 132 29 science science NN cord-311035-s3tkbh9r 132 30 High high JJ cord-311035-s3tkbh9r 132 31 - - HYPH cord-311035-s3tkbh9r 132 32 resolution resolution NN cord-311035-s3tkbh9r 132 33 mapping mapping NN cord-311035-s3tkbh9r 132 34 of of IN cord-311035-s3tkbh9r 132 35 protein protein NN cord-311035-s3tkbh9r 132 36 sequence sequence NN cord-311035-s3tkbh9r 132 37 - - HYPH cord-311035-s3tkbh9r 132 38 function function NN cord-311035-s3tkbh9r 132 39 relationships relationship NNS cord-311035-s3tkbh9r 133 1 A a DT cord-311035-s3tkbh9r 133 2 fundamental fundamental JJ cord-311035-s3tkbh9r 133 3 protein protein NN cord-311035-s3tkbh9r 133 4 property property NN cord-311035-s3tkbh9r 133 5 , , , cord-311035-s3tkbh9r 133 6 thermodynamic thermodynamic JJ cord-311035-s3tkbh9r 133 7 stability stability NN cord-311035-s3tkbh9r 133 8 , , , cord-311035-s3tkbh9r 133 9 revealed reveal VBD cord-311035-s3tkbh9r 133 10 solely solely RB cord-311035-s3tkbh9r 133 11 from from IN cord-311035-s3tkbh9r 133 12 large large JJ cord-311035-s3tkbh9r 133 13 - - HYPH cord-311035-s3tkbh9r 133 14 scale scale NN cord-311035-s3tkbh9r 133 15 measurements measurement NNS cord-311035-s3tkbh9r 133 16 of of IN cord-311035-s3tkbh9r 133 17 protein protein NN cord-311035-s3tkbh9r 133 18 function function NN cord-311035-s3tkbh9r 134 1 Deep deep JJ cord-311035-s3tkbh9r 134 2 mutational mutational JJ cord-311035-s3tkbh9r 134 3 scanning scanning NN cord-311035-s3tkbh9r 134 4 of of IN cord-311035-s3tkbh9r 134 5 an an DT cord-311035-s3tkbh9r 134 6 antibody antibody NN cord-311035-s3tkbh9r 134 7 against against IN cord-311035-s3tkbh9r 134 8 epidermal epidermal JJ cord-311035-s3tkbh9r 134 9 growth growth NN cord-311035-s3tkbh9r 134 10 factor factor NN cord-311035-s3tkbh9r 134 11 receptor receptor NN cord-311035-s3tkbh9r 134 12 using use VBG cord-311035-s3tkbh9r 134 13 mammalian mammalian JJ cord-311035-s3tkbh9r 134 14 cell cell NN cord-311035-s3tkbh9r 134 15 display display NN cord-311035-s3tkbh9r 134 16 and and CC cord-311035-s3tkbh9r 134 17 massively massively RB cord-311035-s3tkbh9r 134 18 parallel parallel JJ cord-311035-s3tkbh9r 134 19 pyrosequencing pyrosequencing NN cord-311035-s3tkbh9r 134 20 Affinity affinity NN cord-311035-s3tkbh9r 134 21 and and CC cord-311035-s3tkbh9r 134 22 cross cross JJ cord-311035-s3tkbh9r 134 23 - - JJ cord-311035-s3tkbh9r 134 24 reactivity reactivity JJ cord-311035-s3tkbh9r 134 25 engineering engineering NN cord-311035-s3tkbh9r 134 26 of of IN cord-311035-s3tkbh9r 134 27 CTLA4-Ig CTLA4-Ig NNP cord-311035-s3tkbh9r 134 28 to to TO cord-311035-s3tkbh9r 134 29 modulate modulate VB cord-311035-s3tkbh9r 134 30 T T NNP cord-311035-s3tkbh9r 134 31 cell cell NN cord-311035-s3tkbh9r 134 32 costimulation costimulation NN cord-311035-s3tkbh9r 135 1 An an DT cord-311035-s3tkbh9r 135 2 engineered engineer VBN cord-311035-s3tkbh9r 135 3 switch switch NN cord-311035-s3tkbh9r 135 4 in in IN cord-311035-s3tkbh9r 135 5 T T NNP cord-311035-s3tkbh9r 135 6 cell cell NN cord-311035-s3tkbh9r 135 7 receptor receptor NN cord-311035-s3tkbh9r 135 8 specificity specificity NN cord-311035-s3tkbh9r 135 9 leads lead VBZ cord-311035-s3tkbh9r 135 10 to to IN cord-311035-s3tkbh9r 135 11 an an DT cord-311035-s3tkbh9r 135 12 unusual unusual JJ cord-311035-s3tkbh9r 135 13 but but CC cord-311035-s3tkbh9r 135 14 functional functional JJ cord-311035-s3tkbh9r 135 15 binding binding NN cord-311035-s3tkbh9r 135 16 geometry geometry NN cord-311035-s3tkbh9r 135 17 Computational computational JJ cord-311035-s3tkbh9r 135 18 design design NN cord-311035-s3tkbh9r 135 19 of of IN cord-311035-s3tkbh9r 135 20 a a DT cord-311035-s3tkbh9r 135 21 protein protein NN cord-311035-s3tkbh9r 135 22 - - HYPH cord-311035-s3tkbh9r 135 23 based base VBN cord-311035-s3tkbh9r 135 24 enzyme enzyme NN cord-311035-s3tkbh9r 135 25 inhibitor inhibitor NN cord-311035-s3tkbh9r 135 26 Experimental experimental JJ cord-311035-s3tkbh9r 135 27 estimation estimation NN cord-311035-s3tkbh9r 135 28 of of IN cord-311035-s3tkbh9r 135 29 the the DT cord-311035-s3tkbh9r 135 30 effects effect NNS cord-311035-s3tkbh9r 135 31 of of IN cord-311035-s3tkbh9r 135 32 all all DT cord-311035-s3tkbh9r 135 33 amino amino NN cord-311035-s3tkbh9r 135 34 - - HYPH cord-311035-s3tkbh9r 135 35 acid acid NN cord-311035-s3tkbh9r 135 36 mutations mutation NNS cord-311035-s3tkbh9r 135 37 to to IN cord-311035-s3tkbh9r 135 38 HIV HIV NNP cord-311035-s3tkbh9r 135 39 's 's POS cord-311035-s3tkbh9r 135 40 envelope envelope NN cord-311035-s3tkbh9r 135 41 protein protein NN cord-311035-s3tkbh9r 135 42 on on IN cord-311035-s3tkbh9r 135 43 viral viral JJ cord-311035-s3tkbh9r 135 44 replication replication NN cord-311035-s3tkbh9r 135 45 in in IN cord-311035-s3tkbh9r 135 46 cell cell NN cord-311035-s3tkbh9r 135 47 culture culture NN cord-311035-s3tkbh9r 136 1 A a DT cord-311035-s3tkbh9r 136 2 platform platform NN cord-311035-s3tkbh9r 136 3 for for IN cord-311035-s3tkbh9r 136 4 functional functional JJ cord-311035-s3tkbh9r 136 5 assessment assessment NN cord-311035-s3tkbh9r 136 6 of of IN cord-311035-s3tkbh9r 136 7 large large JJ cord-311035-s3tkbh9r 136 8 variant variant JJ cord-311035-s3tkbh9r 136 9 libraries library NNS cord-311035-s3tkbh9r 136 10 in in IN cord-311035-s3tkbh9r 136 11 mammalian mammalian JJ cord-311035-s3tkbh9r 136 12 cells cell NNS cord-311035-s3tkbh9r 136 13 Multiplex multiplex JJ cord-311035-s3tkbh9r 136 14 assessment assessment NN cord-311035-s3tkbh9r 136 15 of of IN cord-311035-s3tkbh9r 136 16 protein protein NN cord-311035-s3tkbh9r 136 17 variant variant NN cord-311035-s3tkbh9r 136 18 abundance abundance NN cord-311035-s3tkbh9r 136 19 by by IN cord-311035-s3tkbh9r 136 20 massively massively RB cord-311035-s3tkbh9r 136 21 parallel parallel JJ cord-311035-s3tkbh9r 136 22 sequencing sequencing NN cord-311035-s3tkbh9r 136 23 Mapping mapping NN cord-311035-s3tkbh9r 136 24 interaction interaction NN cord-311035-s3tkbh9r 136 25 sites site NNS cord-311035-s3tkbh9r 136 26 on on IN cord-311035-s3tkbh9r 136 27 human human JJ cord-311035-s3tkbh9r 136 28 chemokine chemokine NN cord-311035-s3tkbh9r 136 29 receptors receptor NNS cord-311035-s3tkbh9r 136 30 by by IN cord-311035-s3tkbh9r 136 31 deep deep JJ cord-311035-s3tkbh9r 136 32 mutational mutational JJ cord-311035-s3tkbh9r 136 33 scanning scanning NN cord-311035-s3tkbh9r 136 34 This this DT cord-311035-s3tkbh9r 136 35 study study NN cord-311035-s3tkbh9r 136 36 established establish VBD cord-311035-s3tkbh9r 136 37 a a DT cord-311035-s3tkbh9r 136 38 simple simple JJ cord-311035-s3tkbh9r 136 39 and and CC cord-311035-s3tkbh9r 136 40 effective effective JJ cord-311035-s3tkbh9r 136 41 method method NN cord-311035-s3tkbh9r 136 42 for for IN cord-311035-s3tkbh9r 136 43 linking link VBG cord-311035-s3tkbh9r 136 44 phenotype phenotype NN cord-311035-s3tkbh9r 136 45 to to IN cord-311035-s3tkbh9r 136 46 a a DT cord-311035-s3tkbh9r 136 47 single single JJ cord-311035-s3tkbh9r 136 48 genotype genotype NN cord-311035-s3tkbh9r 136 49 in in IN cord-311035-s3tkbh9r 136 50 transfected transfecte VBN cord-311035-s3tkbh9r 136 51 human human JJ cord-311035-s3tkbh9r 136 52 cells cell NNS cord-311035-s3tkbh9r 136 53 . . . cord-311035-s3tkbh9r 137 1 This this DT cord-311035-s3tkbh9r 137 2 technical technical JJ cord-311035-s3tkbh9r 137 3 accomplishment accomplishment NN cord-311035-s3tkbh9r 137 4 is be VBZ cord-311035-s3tkbh9r 137 5 necessary necessary JJ cord-311035-s3tkbh9r 137 6 for for IN cord-311035-s3tkbh9r 137 7 selection selection NN cord-311035-s3tkbh9r 137 8 and and CC cord-311035-s3tkbh9r 137 9 deep deep JJ cord-311035-s3tkbh9r 137 10 mutational mutational JJ cord-311035-s3tkbh9r 137 11 scanning scanning NN cord-311035-s3tkbh9r 137 12 in in IN cord-311035-s3tkbh9r 137 13 human human JJ cord-311035-s3tkbh9r 137 14 cells cell NNS cord-311035-s3tkbh9r 138 1 A a DT cord-311035-s3tkbh9r 138 2 comprehensive comprehensive JJ cord-311035-s3tkbh9r 138 3 biophysical biophysical JJ cord-311035-s3tkbh9r 138 4 description description NN cord-311035-s3tkbh9r 138 5 of of IN cord-311035-s3tkbh9r 138 6 pairwise pairwise FW cord-311035-s3tkbh9r 138 7 epistasis epistasis NN cord-311035-s3tkbh9r 138 8 throughout throughout IN cord-311035-s3tkbh9r 138 9 an an DT cord-311035-s3tkbh9r 138 10 entire entire JJ cord-311035-s3tkbh9r 138 11 protein protein NN cord-311035-s3tkbh9r 138 12 domain domain NN cord-311035-s3tkbh9r 138 13 High high JJ cord-311035-s3tkbh9r 138 14 - - HYPH cord-311035-s3tkbh9r 138 15 throughput throughput NN cord-311035-s3tkbh9r 138 16 profiling profiling NN cord-311035-s3tkbh9r 138 17 of of IN cord-311035-s3tkbh9r 138 18 influenza influenza NN cord-311035-s3tkbh9r 138 19 A a DT cord-311035-s3tkbh9r 138 20 virus virus NN cord-311035-s3tkbh9r 138 21 hemagglutinin hemagglutinin NN cord-311035-s3tkbh9r 138 22 gene gene NN cord-311035-s3tkbh9r 138 23 at at IN cord-311035-s3tkbh9r 138 24 single single JJ cord-311035-s3tkbh9r 138 25 - - HYPH cord-311035-s3tkbh9r 138 26 nucleotide nucleotide NN cord-311035-s3tkbh9r 138 27 resolution resolution NN cord-311035-s3tkbh9r 138 28 Deep deep JJ cord-311035-s3tkbh9r 138 29 mutational mutational JJ cord-311035-s3tkbh9r 138 30 scanning scanning NN cord-311035-s3tkbh9r 138 31 of of IN cord-311035-s3tkbh9r 138 32 SARS SARS NNP cord-311035-s3tkbh9r 138 33 - - HYPH cord-311035-s3tkbh9r 138 34 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 138 35 receptor receptor NN cord-311035-s3tkbh9r 138 36 binding bind VBG cord-311035-s3tkbh9r 138 37 domain domain NN cord-311035-s3tkbh9r 138 38 reveals reveal VBZ cord-311035-s3tkbh9r 138 39 constraints constraint NNS cord-311035-s3tkbh9r 138 40 on on IN cord-311035-s3tkbh9r 138 41 folding fold VBG cord-311035-s3tkbh9r 138 42 and and CC cord-311035-s3tkbh9r 138 43 ACE2 ACE2 NNP cord-311035-s3tkbh9r 138 44 binding binding NN cord-311035-s3tkbh9r 139 1 The the DT cord-311035-s3tkbh9r 139 2 isolated isolated JJ cord-311035-s3tkbh9r 139 3 RBD RBD NNP cord-311035-s3tkbh9r 139 4 of of IN cord-311035-s3tkbh9r 139 5 SARS SARS NNP cord-311035-s3tkbh9r 139 6 - - HYPH cord-311035-s3tkbh9r 139 7 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 139 8 was be VBD cord-311035-s3tkbh9r 139 9 displayed display VBN cord-311035-s3tkbh9r 139 10 on on IN cord-311035-s3tkbh9r 139 11 yeast yeast NN cord-311035-s3tkbh9r 139 12 and and CC cord-311035-s3tkbh9r 139 13 deep deep JJ cord-311035-s3tkbh9r 139 14 mutationally mutationally RB cord-311035-s3tkbh9r 139 15 scanned scan VBN cord-311035-s3tkbh9r 139 16 to to TO cord-311035-s3tkbh9r 139 17 understand understand VB cord-311035-s3tkbh9r 139 18 the the DT cord-311035-s3tkbh9r 139 19 mutational mutational JJ cord-311035-s3tkbh9r 139 20 landscape landscape NN cord-311035-s3tkbh9r 139 21 for for IN cord-311035-s3tkbh9r 139 22 yeast yeast NN cord-311035-s3tkbh9r 139 23 surface surface NN cord-311035-s3tkbh9r 139 24 expression expression NN cord-311035-s3tkbh9r 139 25 ( ( -LRB- cord-311035-s3tkbh9r 139 26 a a DT cord-311035-s3tkbh9r 139 27 surrogate surrogate NN cord-311035-s3tkbh9r 139 28 for for IN cord-311035-s3tkbh9r 139 29 folding fold VBG cord-311035-s3tkbh9r 139 30 ) ) -RRB- cord-311035-s3tkbh9r 139 31 and and CC cord-311035-s3tkbh9r 139 32 ACE2 ACE2 NNP cord-311035-s3tkbh9r 139 33 binding binding NN cord-311035-s3tkbh9r 139 34 . . . cord-311035-s3tkbh9r 140 1 The the DT cord-311035-s3tkbh9r 140 2 data datum NNS cord-311035-s3tkbh9r 140 3 reveal reveal VBP cord-311035-s3tkbh9r 140 4 substantial substantial JJ cord-311035-s3tkbh9r 140 5 sequence sequence NN cord-311035-s3tkbh9r 140 6 diversity diversity NN cord-311035-s3tkbh9r 140 7 is be VBZ cord-311035-s3tkbh9r 140 8 tolerated tolerate VBN cord-311035-s3tkbh9r 140 9 on on IN cord-311035-s3tkbh9r 140 10 the the DT cord-311035-s3tkbh9r 140 11 RBD RBD NNP cord-311035-s3tkbh9r 140 12 surface surface NN cord-311035-s3tkbh9r 140 13 Engineering Engineering NNP cord-311035-s3tkbh9r 140 14 human human JJ cord-311035-s3tkbh9r 140 15 ACE2 ACE2 NNP cord-311035-s3tkbh9r 140 16 to to TO cord-311035-s3tkbh9r 140 17 optimize optimize VB cord-311035-s3tkbh9r 140 18 binding bind VBG cord-311035-s3tkbh9r 140 19 to to IN cord-311035-s3tkbh9r 140 20 the the DT cord-311035-s3tkbh9r 140 21 spike spike NN cord-311035-s3tkbh9r 140 22 protein protein NN cord-311035-s3tkbh9r 140 23 of of IN cord-311035-s3tkbh9r 140 24 SARS SARS NNP cord-311035-s3tkbh9r 140 25 coronavirus coronavirus NN cord-311035-s3tkbh9r 141 1 2 2 LS cord-311035-s3tkbh9r 141 2 deep deep JJ cord-311035-s3tkbh9r 141 3 mutationally mutationally RB cord-311035-s3tkbh9r 141 4 scanned scan VBN cord-311035-s3tkbh9r 141 5 ACE2 ACE2 NNP cord-311035-s3tkbh9r 141 6 expressed express VBD cord-311035-s3tkbh9r 141 7 on on IN cord-311035-s3tkbh9r 141 8 a a DT cord-311035-s3tkbh9r 141 9 human human JJ cord-311035-s3tkbh9r 141 10 cell cell NN cord-311035-s3tkbh9r 141 11 membrane membrane NN cord-311035-s3tkbh9r 141 12 to to TO cord-311035-s3tkbh9r 141 13 identify identify VB cord-311035-s3tkbh9r 141 14 substitutions substitution NNS cord-311035-s3tkbh9r 141 15 that that WDT cord-311035-s3tkbh9r 141 16 enhance enhance VBP cord-311035-s3tkbh9r 141 17 binding binding NN cord-311035-s3tkbh9r 141 18 to to IN cord-311035-s3tkbh9r 141 19 S S NNP cord-311035-s3tkbh9r 141 20 of of IN cord-311035-s3tkbh9r 141 21 SARS SARS NNP cord-311035-s3tkbh9r 141 22 - - HYPH cord-311035-s3tkbh9r 141 23 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 141 24 . . . cord-311035-s3tkbh9r 142 1 This this DT cord-311035-s3tkbh9r 142 2 guided guide VBD cord-311035-s3tkbh9r 142 3 the the DT cord-311035-s3tkbh9r 142 4 engineering engineering NN cord-311035-s3tkbh9r 142 5 of of IN cord-311035-s3tkbh9r 142 6 high high JJ cord-311035-s3tkbh9r 142 7 affinity affinity NN cord-311035-s3tkbh9r 142 8 and and CC cord-311035-s3tkbh9r 142 9 potently potently RB cord-311035-s3tkbh9r 142 10 neutralizing neutralize VBG cord-311035-s3tkbh9r 142 11 decoy decoy NN cord-311035-s3tkbh9r 142 12 receptors receptor NNS cord-311035-s3tkbh9r 142 13 Global global JJ cord-311035-s3tkbh9r 142 14 analysis analysis NN cord-311035-s3tkbh9r 142 15 of of IN cord-311035-s3tkbh9r 142 16 protein protein NN cord-311035-s3tkbh9r 142 17 folding folding NN cord-311035-s3tkbh9r 142 18 using use VBG cord-311035-s3tkbh9r 142 19 massively massively RB cord-311035-s3tkbh9r 142 20 parallel parallel JJ cord-311035-s3tkbh9r 142 21 design design NN cord-311035-s3tkbh9r 142 22 , , , cord-311035-s3tkbh9r 142 23 synthesis synthesis NN cord-311035-s3tkbh9r 142 24 , , , cord-311035-s3tkbh9r 142 25 and and CC cord-311035-s3tkbh9r 142 26 testing test VBG cord-311035-s3tkbh9r 142 27 A a DT cord-311035-s3tkbh9r 142 28 computationally computationally RB cord-311035-s3tkbh9r 142 29 designed design VBN cord-311035-s3tkbh9r 142 30 inhibitor inhibitor NN cord-311035-s3tkbh9r 142 31 of of IN cord-311035-s3tkbh9r 142 32 an an DT cord-311035-s3tkbh9r 142 33 Epstein Epstein NNP cord-311035-s3tkbh9r 142 34 - - HYPH cord-311035-s3tkbh9r 142 35 Barr Barr NNP cord-311035-s3tkbh9r 142 36 viral viral NN cord-311035-s3tkbh9r 143 1 Bcl-2 Bcl-2 NNP cord-311035-s3tkbh9r 143 2 protein protein NN cord-311035-s3tkbh9r 143 3 induces induce VBZ cord-311035-s3tkbh9r 143 4 apoptosis apoptosis NN cord-311035-s3tkbh9r 143 5 in in IN cord-311035-s3tkbh9r 143 6 infected infected JJ cord-311035-s3tkbh9r 143 7 cells cell NNS cord-311035-s3tkbh9r 144 1 Computationally computationally RB cord-311035-s3tkbh9r 144 2 designed design VBN cord-311035-s3tkbh9r 144 3 high high JJ cord-311035-s3tkbh9r 144 4 specificity specificity NN cord-311035-s3tkbh9r 144 5 inhibitors inhibitor NNS cord-311035-s3tkbh9r 144 6 delineate delineate VBP cord-311035-s3tkbh9r 144 7 the the DT cord-311035-s3tkbh9r 144 8 roles role NNS cord-311035-s3tkbh9r 144 9 of of IN cord-311035-s3tkbh9r 144 10 BCL2 BCL2 NNP cord-311035-s3tkbh9r 144 11 family family NN cord-311035-s3tkbh9r 144 12 proteins protein NNS cord-311035-s3tkbh9r 144 13 in in IN cord-311035-s3tkbh9r 144 14 cancer cancer NN cord-311035-s3tkbh9r 144 15 Engineered engineer VBN cord-311035-s3tkbh9r 144 16 receptors receptor NNS cord-311035-s3tkbh9r 144 17 for for IN cord-311035-s3tkbh9r 144 18 human human JJ cord-311035-s3tkbh9r 144 19 cytomegalovirus cytomegalovirus NN cord-311035-s3tkbh9r 144 20 that that WDT cord-311035-s3tkbh9r 144 21 are be VBP cord-311035-s3tkbh9r 144 22 orthogonal orthogonal JJ cord-311035-s3tkbh9r 144 23 to to IN cord-311035-s3tkbh9r 144 24 normal normal JJ cord-311035-s3tkbh9r 144 25 human human JJ cord-311035-s3tkbh9r 144 26 biology biology NN cord-311035-s3tkbh9r 144 27 Single single JJ cord-311035-s3tkbh9r 144 28 - - HYPH cord-311035-s3tkbh9r 144 29 mutation mutation NN cord-311035-s3tkbh9r 144 30 fitness fitness NN cord-311035-s3tkbh9r 144 31 landscapes landscape NNS cord-311035-s3tkbh9r 144 32 for for IN cord-311035-s3tkbh9r 144 33 an an DT cord-311035-s3tkbh9r 144 34 enzyme enzyme NN cord-311035-s3tkbh9r 144 35 on on IN cord-311035-s3tkbh9r 144 36 multiple multiple JJ cord-311035-s3tkbh9r 144 37 substrates substrate NNS cord-311035-s3tkbh9r 145 1 reveal reveal VB cord-311035-s3tkbh9r 145 2 specificity specificity NN cord-311035-s3tkbh9r 145 3 is be VBZ cord-311035-s3tkbh9r 145 4 globally globally RB cord-311035-s3tkbh9r 145 5 encoded encode VBN cord-311035-s3tkbh9r 145 6 A a DT cord-311035-s3tkbh9r 145 7 comprehensive comprehensive JJ cord-311035-s3tkbh9r 145 8 , , , cord-311035-s3tkbh9r 145 9 highresolution highresolution NNP cord-311035-s3tkbh9r 145 10 map map NN cord-311035-s3tkbh9r 145 11 of of IN cord-311035-s3tkbh9r 145 12 a a DT cord-311035-s3tkbh9r 145 13 gene gene NN cord-311035-s3tkbh9r 145 14 's 's POS cord-311035-s3tkbh9r 145 15 fitness fitness NN cord-311035-s3tkbh9r 145 16 landscape landscape NN cord-311035-s3tkbh9r 145 17 Comprehensive comprehensive JJ cord-311035-s3tkbh9r 145 18 sequence sequence NN cord-311035-s3tkbh9r 145 19 - - HYPH cord-311035-s3tkbh9r 145 20 flux flux NN cord-311035-s3tkbh9r 145 21 mapping mapping NN cord-311035-s3tkbh9r 145 22 of of IN cord-311035-s3tkbh9r 145 23 a a DT cord-311035-s3tkbh9r 145 24 levoglucosan levoglucosan NNP cord-311035-s3tkbh9r 145 25 utilization utilization NN cord-311035-s3tkbh9r 145 26 pathway pathway NN cord-311035-s3tkbh9r 145 27 in in IN cord-311035-s3tkbh9r 145 28 E. E. NNP cord-311035-s3tkbh9r 145 29 coli coli VBZ cord-311035-s3tkbh9r 145 30 Molecular molecular JJ cord-311035-s3tkbh9r 145 31 determinants determinant NNS cord-311035-s3tkbh9r 145 32 of of IN cord-311035-s3tkbh9r 145 33 chaperone chaperone NN cord-311035-s3tkbh9r 145 34 interactions interaction NNS cord-311035-s3tkbh9r 145 35 on on IN cord-311035-s3tkbh9r 145 36 MHC MHC NNP cord-311035-s3tkbh9r 145 37 - - HYPH cord-311035-s3tkbh9r 145 38 I I NNP cord-311035-s3tkbh9r 145 39 for for IN cord-311035-s3tkbh9r 145 40 folding folding NN cord-311035-s3tkbh9r 145 41 and and CC cord-311035-s3tkbh9r 145 42 antigen antigen NN cord-311035-s3tkbh9r 145 43 repertoire repertoire NN cord-311035-s3tkbh9r 146 1 selection selection NNP cord-311035-s3tkbh9r 146 2 Cross cross NN cord-311035-s3tkbh9r 146 3 - - NN cord-311035-s3tkbh9r 146 4 neutralization neutralization NN cord-311035-s3tkbh9r 146 5 of of IN cord-311035-s3tkbh9r 146 6 SARS SARS NNP cord-311035-s3tkbh9r 146 7 - - HYPH cord-311035-s3tkbh9r 146 8 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 146 9 by by IN cord-311035-s3tkbh9r 146 10 a a DT cord-311035-s3tkbh9r 146 11 human human JJ cord-311035-s3tkbh9r 146 12 monoclonal monoclonal JJ cord-311035-s3tkbh9r 146 13 SARS SARS NNP cord-311035-s3tkbh9r 146 14 - - HYPH cord-311035-s3tkbh9r 146 15 CoV CoV NNP cord-311035-s3tkbh9r 146 16 antibody antibody NN cord-311035-s3tkbh9r 146 17 Studies Studies NNPS cord-311035-s3tkbh9r 146 18 in in IN cord-311035-s3tkbh9r 146 19 humanized humanized JJ cord-311035-s3tkbh9r 146 20 mice mouse NNS cord-311035-s3tkbh9r 146 21 and and CC cord-311035-s3tkbh9r 146 22 convalescent convalescent JJ cord-311035-s3tkbh9r 146 23 humans human NNS cord-311035-s3tkbh9r 146 24 yield yield VBP cord-311035-s3tkbh9r 146 25 a a DT cord-311035-s3tkbh9r 146 26 SARS SARS NNP cord-311035-s3tkbh9r 146 27 - - HYPH cord-311035-s3tkbh9r 146 28 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 146 29 antibody antibody NN cord-311035-s3tkbh9r 146 30 cocktail cocktail NN cord-311035-s3tkbh9r 146 31 Potent potent JJ cord-311035-s3tkbh9r 146 32 neutralizing neutralize VBG cord-311035-s3tkbh9r 146 33 antibodies antibody NNS cord-311035-s3tkbh9r 146 34 from from IN cord-311035-s3tkbh9r 146 35 COVID-19 covid-19 JJ cord-311035-s3tkbh9r 146 36 patients patient NNS cord-311035-s3tkbh9r 146 37 define define VBP cord-311035-s3tkbh9r 146 38 multiple multiple JJ cord-311035-s3tkbh9r 146 39 targets target NNS cord-311035-s3tkbh9r 146 40 of of IN cord-311035-s3tkbh9r 146 41 vulnerability vulnerability NN cord-311035-s3tkbh9r 146 42 Broad broad JJ cord-311035-s3tkbh9r 146 43 neutralization neutralization NN cord-311035-s3tkbh9r 146 44 of of IN cord-311035-s3tkbh9r 146 45 SARS SARS NNP cord-311035-s3tkbh9r 146 46 - - HYPH cord-311035-s3tkbh9r 146 47 related relate VBN cord-311035-s3tkbh9r 146 48 viruses virus NNS cord-311035-s3tkbh9r 146 49 by by IN cord-311035-s3tkbh9r 146 50 human human JJ cord-311035-s3tkbh9r 146 51 monoclonal monoclonal JJ cord-311035-s3tkbh9r 146 52 antibodies antibody NNS cord-311035-s3tkbh9r 147 1 A a DT cord-311035-s3tkbh9r 147 2 human human JJ cord-311035-s3tkbh9r 147 3 monoclonal monoclonal JJ cord-311035-s3tkbh9r 147 4 antibody antibody NN cord-311035-s3tkbh9r 147 5 blocking block VBG cord-311035-s3tkbh9r 147 6 SARS SARS NNP cord-311035-s3tkbh9r 147 7 - - HYPH cord-311035-s3tkbh9r 147 8 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 147 9 infection infection NN cord-311035-s3tkbh9r 148 1 A a DT cord-311035-s3tkbh9r 148 2 noncompeting noncompeting JJ cord-311035-s3tkbh9r 148 3 pair pair NN cord-311035-s3tkbh9r 148 4 of of IN cord-311035-s3tkbh9r 148 5 human human JJ cord-311035-s3tkbh9r 148 6 neutralizing neutralize VBG cord-311035-s3tkbh9r 148 7 antibodies antibody NNS cord-311035-s3tkbh9r 148 8 block block VBP cord-311035-s3tkbh9r 148 9 COVID-19 COVID-19 NNP cord-311035-s3tkbh9r 148 10 virus virus NN cord-311035-s3tkbh9r 148 11 binding bind VBG cord-311035-s3tkbh9r 148 12 to to IN cord-311035-s3tkbh9r 148 13 its -PRON- PRP$ cord-311035-s3tkbh9r 148 14 receptor receptor NN cord-311035-s3tkbh9r 148 15 ACE2 ACE2 NNP cord-311035-s3tkbh9r 148 16 Isolation Isolation NNP cord-311035-s3tkbh9r 148 17 of of IN cord-311035-s3tkbh9r 148 18 potent potent JJ cord-311035-s3tkbh9r 148 19 SARS SARS NNP cord-311035-s3tkbh9r 148 20 - - HYPH cord-311035-s3tkbh9r 148 21 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 148 22 neutralizing neutralize VBG cord-311035-s3tkbh9r 148 23 antibodies antibody NNS cord-311035-s3tkbh9r 148 24 and and CC cord-311035-s3tkbh9r 148 25 protection protection NN cord-311035-s3tkbh9r 148 26 from from IN cord-311035-s3tkbh9r 148 27 disease disease NN cord-311035-s3tkbh9r 148 28 in in IN cord-311035-s3tkbh9r 148 29 a a DT cord-311035-s3tkbh9r 148 30 small small JJ cord-311035-s3tkbh9r 148 31 animal animal NN cord-311035-s3tkbh9r 148 32 model model NN cord-311035-s3tkbh9r 148 33 Structure Structure NNP cord-311035-s3tkbh9r 148 34 , , , cord-311035-s3tkbh9r 148 35 function function NN cord-311035-s3tkbh9r 148 36 , , , cord-311035-s3tkbh9r 148 37 and and CC cord-311035-s3tkbh9r 148 38 antigenicity antigenicity NN cord-311035-s3tkbh9r 148 39 of of IN cord-311035-s3tkbh9r 148 40 the the DT cord-311035-s3tkbh9r 148 41 SARS SARS NNP cord-311035-s3tkbh9r 148 42 - - HYPH cord-311035-s3tkbh9r 148 43 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 148 44 spike spike NN cord-311035-s3tkbh9r 148 45 glycoprotein glycoprotein NN cord-311035-s3tkbh9r 148 46 Structural structural JJ cord-311035-s3tkbh9r 148 47 insights insight NNS cord-311035-s3tkbh9r 148 48 into into IN cord-311035-s3tkbh9r 148 49 coronavirus coronavirus NN cord-311035-s3tkbh9r 148 50 entry entry NN cord-311035-s3tkbh9r 148 51 SARS SARS NNP cord-311035-s3tkbh9r 148 52 - - HYPH cord-311035-s3tkbh9r 148 53 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 148 54 cell cell NN cord-311035-s3tkbh9r 148 55 entry entry NN cord-311035-s3tkbh9r 148 56 depends depend VBZ cord-311035-s3tkbh9r 148 57 on on IN cord-311035-s3tkbh9r 148 58 ACE2 ACE2 NNP cord-311035-s3tkbh9r 148 59 and and CC cord-311035-s3tkbh9r 148 60 TMPRSS2 TMPRSS2 NNP cord-311035-s3tkbh9r 148 61 and and CC cord-311035-s3tkbh9r 148 62 is be VBZ cord-311035-s3tkbh9r 148 63 blocked block VBN cord-311035-s3tkbh9r 148 64 by by IN cord-311035-s3tkbh9r 148 65 a a DT cord-311035-s3tkbh9r 148 66 clinically clinically RB cord-311035-s3tkbh9r 148 67 proven prove VBN cord-311035-s3tkbh9r 148 68 protease protease NN cord-311035-s3tkbh9r 148 69 inhibitor inhibitor NN cord-311035-s3tkbh9r 149 1 A a DT cord-311035-s3tkbh9r 149 2 pneumonia pneumonia NN cord-311035-s3tkbh9r 149 3 outbreak outbreak NN cord-311035-s3tkbh9r 149 4 associated associate VBN cord-311035-s3tkbh9r 149 5 with with IN cord-311035-s3tkbh9r 149 6 a a DT cord-311035-s3tkbh9r 149 7 new new JJ cord-311035-s3tkbh9r 149 8 coronavirus coronavirus NN cord-311035-s3tkbh9r 149 9 of of IN cord-311035-s3tkbh9r 149 10 probable probable JJ cord-311035-s3tkbh9r 149 11 bat bat NN cord-311035-s3tkbh9r 149 12 origin origin NN cord-311035-s3tkbh9r 149 13 Receptor receptor NN cord-311035-s3tkbh9r 149 14 recognition recognition NN cord-311035-s3tkbh9r 149 15 by by IN cord-311035-s3tkbh9r 149 16 the the DT cord-311035-s3tkbh9r 149 17 novel novel JJ cord-311035-s3tkbh9r 149 18 coronavirus coronavirus NN cord-311035-s3tkbh9r 149 19 from from IN cord-311035-s3tkbh9r 149 20 Wuhan Wuhan NNP cord-311035-s3tkbh9r 149 21 : : : cord-311035-s3tkbh9r 149 22 an an DT cord-311035-s3tkbh9r 149 23 analysis analysis NN cord-311035-s3tkbh9r 149 24 based base VBN cord-311035-s3tkbh9r 149 25 on on IN cord-311035-s3tkbh9r 149 26 decade decade NN cord-311035-s3tkbh9r 149 27 - - HYPH cord-311035-s3tkbh9r 149 28 long long JJ cord-311035-s3tkbh9r 149 29 structural structural JJ cord-311035-s3tkbh9r 149 30 studies study NNS cord-311035-s3tkbh9r 149 31 of of IN cord-311035-s3tkbh9r 149 32 SARS SARS NNP cord-311035-s3tkbh9r 149 33 Cryo Cryo NNP cord-311035-s3tkbh9r 149 34 - - HYPH cord-311035-s3tkbh9r 149 35 EM EM NNP cord-311035-s3tkbh9r 149 36 structure structure NN cord-311035-s3tkbh9r 149 37 of of IN cord-311035-s3tkbh9r 149 38 the the DT cord-311035-s3tkbh9r 149 39 2019-nCoV 2019-ncov CD cord-311035-s3tkbh9r 149 40 spike spike NN cord-311035-s3tkbh9r 149 41 in in IN cord-311035-s3tkbh9r 149 42 the the DT cord-311035-s3tkbh9r 149 43 prefusion prefusion NN cord-311035-s3tkbh9r 149 44 conformation conformation NN cord-311035-s3tkbh9r 149 45 Angiotensin Angiotensin NNP cord-311035-s3tkbh9r 149 46 - - HYPH cord-311035-s3tkbh9r 149 47 converting convert VBG cord-311035-s3tkbh9r 149 48 enzyme enzyme NN cord-311035-s3tkbh9r 149 49 2 2 CD cord-311035-s3tkbh9r 149 50 is be VBZ cord-311035-s3tkbh9r 149 51 a a DT cord-311035-s3tkbh9r 149 52 functional functional JJ cord-311035-s3tkbh9r 149 53 receptor receptor NN cord-311035-s3tkbh9r 149 54 for for IN cord-311035-s3tkbh9r 149 55 the the DT cord-311035-s3tkbh9r 149 56 SARS SARS NNP cord-311035-s3tkbh9r 149 57 coronavirus coronavirus NN cord-311035-s3tkbh9r 150 1 This this DT cord-311035-s3tkbh9r 150 2 study study NN cord-311035-s3tkbh9r 150 3 reports report VBZ cord-311035-s3tkbh9r 150 4 the the DT cord-311035-s3tkbh9r 150 5 original original JJ cord-311035-s3tkbh9r 150 6 discovery discovery NN cord-311035-s3tkbh9r 150 7 of of IN cord-311035-s3tkbh9r 150 8 ACE2 ACE2 NNP cord-311035-s3tkbh9r 150 9 as as IN cord-311035-s3tkbh9r 150 10 the the DT cord-311035-s3tkbh9r 150 11 entry entry NN cord-311035-s3tkbh9r 150 12 receptor receptor NN cord-311035-s3tkbh9r 150 13 for for IN cord-311035-s3tkbh9r 150 14 classical classical JJ cord-311035-s3tkbh9r 150 15 SARS SARS NNP cord-311035-s3tkbh9r 150 16 - - HYPH cord-311035-s3tkbh9r 150 17 CoV-1 CoV-1 NNP cord-311035-s3tkbh9r 150 18 Functional functional JJ cord-311035-s3tkbh9r 150 19 assessment assessment NN cord-311035-s3tkbh9r 150 20 of of IN cord-311035-s3tkbh9r 150 21 cell cell NN cord-311035-s3tkbh9r 150 22 entry entry NN cord-311035-s3tkbh9r 150 23 and and CC cord-311035-s3tkbh9r 150 24 receptor receptor NN cord-311035-s3tkbh9r 150 25 usage usage NN cord-311035-s3tkbh9r 150 26 for for IN cord-311035-s3tkbh9r 150 27 SARS SARS NNP cord-311035-s3tkbh9r 150 28 - - HYPH cord-311035-s3tkbh9r 150 29 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 150 30 and and CC cord-311035-s3tkbh9r 150 31 other other JJ cord-311035-s3tkbh9r 150 32 lineage lineage NN cord-311035-s3tkbh9r 150 33 B b NN cord-311035-s3tkbh9r 150 34 betacoronaviruses betacoronaviruses NNP cord-311035-s3tkbh9r 151 1 * * NFP cord-311035-s3tkbh9r 152 1 ACE2 ACE2 NNP cord-311035-s3tkbh9r 152 2 is be VBZ cord-311035-s3tkbh9r 152 3 shown show VBN cord-311035-s3tkbh9r 152 4 to to TO cord-311035-s3tkbh9r 152 5 be be VB cord-311035-s3tkbh9r 152 6 a a DT cord-311035-s3tkbh9r 152 7 shared share VBN cord-311035-s3tkbh9r 152 8 entry entry NN cord-311035-s3tkbh9r 152 9 receptor receptor NN cord-311035-s3tkbh9r 152 10 for for IN cord-311035-s3tkbh9r 152 11 a a DT cord-311035-s3tkbh9r 152 12 clade clade NN cord-311035-s3tkbh9r 152 13 of of IN cord-311035-s3tkbh9r 152 14 SARS SARS NNP cord-311035-s3tkbh9r 152 15 - - HYPH cord-311035-s3tkbh9r 152 16 associated associate VBN cord-311035-s3tkbh9r 152 17 betacoronaviruses betacoronaviruse NNS cord-311035-s3tkbh9r 152 18 , , , cord-311035-s3tkbh9r 152 19 including include VBG cord-311035-s3tkbh9r 152 20 diverse diverse JJ cord-311035-s3tkbh9r 152 21 strains strain NNS cord-311035-s3tkbh9r 152 22 from from IN cord-311035-s3tkbh9r 152 23 bats bat NNS cord-311035-s3tkbh9r 152 24 and and CC cord-311035-s3tkbh9r 152 25 human human JJ cord-311035-s3tkbh9r 152 26 virus virus NN cord-311035-s3tkbh9r 152 27 SARS SARS NNP cord-311035-s3tkbh9r 152 28 - - HYPH cord-311035-s3tkbh9r 152 29 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 152 30 Susceptibility Susceptibility NNP cord-311035-s3tkbh9r 152 31 to to IN cord-311035-s3tkbh9r 152 32 SARS SARS NNP cord-311035-s3tkbh9r 152 33 coronavirus coronavirus NN cord-311035-s3tkbh9r 152 34 S S NNP cord-311035-s3tkbh9r 152 35 protein protein NN cord-311035-s3tkbh9r 152 36 - - HYPH cord-311035-s3tkbh9r 152 37 driven drive VBN cord-311035-s3tkbh9r 152 38 infection infection NN cord-311035-s3tkbh9r 153 1 correlates correlate VBZ cord-311035-s3tkbh9r 153 2 with with IN cord-311035-s3tkbh9r 153 3 expression expression NN cord-311035-s3tkbh9r 153 4 of of IN cord-311035-s3tkbh9r 153 5 angiotensin angiotensin NN cord-311035-s3tkbh9r 153 6 converting convert VBG cord-311035-s3tkbh9r 153 7 enzyme enzyme NN cord-311035-s3tkbh9r 153 8 2 2 CD cord-311035-s3tkbh9r 153 9 and and CC cord-311035-s3tkbh9r 153 10 infection infection NN cord-311035-s3tkbh9r 153 11 can can MD cord-311035-s3tkbh9r 153 12 be be VB cord-311035-s3tkbh9r 153 13 blocked block VBN cord-311035-s3tkbh9r 153 14 by by IN cord-311035-s3tkbh9r 153 15 soluble soluble JJ cord-311035-s3tkbh9r 153 16 receptor receptor NN cord-311035-s3tkbh9r 153 17 Neutralization neutralization NN cord-311035-s3tkbh9r 153 18 of of IN cord-311035-s3tkbh9r 153 19 SARS SARS NNP cord-311035-s3tkbh9r 153 20 - - HYPH cord-311035-s3tkbh9r 153 21 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 153 22 spike spike NN cord-311035-s3tkbh9r 153 23 pseudotyped pseudotype VBD cord-311035-s3tkbh9r 153 24 virus virus NN cord-311035-s3tkbh9r 153 25 by by IN cord-311035-s3tkbh9r 153 26 recombinant recombinant JJ cord-311035-s3tkbh9r 153 27 ACE2-Ig ACE2-Ig NNP cord-311035-s3tkbh9r 153 28 Inhibition Inhibition NNP cord-311035-s3tkbh9r 153 29 of of IN cord-311035-s3tkbh9r 153 30 SARS SARS NNP cord-311035-s3tkbh9r 153 31 - - HYPH cord-311035-s3tkbh9r 153 32 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 153 33 infections infection NNS cord-311035-s3tkbh9r 153 34 in in IN cord-311035-s3tkbh9r 153 35 engineered engineer VBN cord-311035-s3tkbh9r 153 36 human human JJ cord-311035-s3tkbh9r 153 37 tissues tissue NNS cord-311035-s3tkbh9r 153 38 using use VBG cord-311035-s3tkbh9r 153 39 clinical clinical JJ cord-311035-s3tkbh9r 153 40 - - HYPH cord-311035-s3tkbh9r 153 41 grade grade NN cord-311035-s3tkbh9r 153 42 soluble soluble JJ cord-311035-s3tkbh9r 153 43 human human JJ cord-311035-s3tkbh9r 153 44 ACE2 ACE2 NNP cord-311035-s3tkbh9r 153 45 Novel Novel NNP cord-311035-s3tkbh9r 153 46 ACE2-IgG1 ACE2-IgG1 NNP cord-311035-s3tkbh9r 153 47 fusions fusion NNS cord-311035-s3tkbh9r 153 48 with with IN cord-311035-s3tkbh9r 153 49 improved improve VBN cord-311035-s3tkbh9r 153 50 in in IN cord-311035-s3tkbh9r 153 51 vitro vitro FW cord-311035-s3tkbh9r 153 52 and and CC cord-311035-s3tkbh9r 153 53 in in IN cord-311035-s3tkbh9r 153 54 vivo vivo NN cord-311035-s3tkbh9r 153 55 activity activity NN cord-311035-s3tkbh9r 153 56 against against IN cord-311035-s3tkbh9r 153 57 SARS SARS NNP cord-311035-s3tkbh9r 153 58 - - HYPH cord-311035-s3tkbh9r 153 59 CoV2 CoV2 NNP cord-311035-s3tkbh9r 153 60 Antibody Antibody NNP cord-311035-s3tkbh9r 153 61 cocktail cocktail NN cord-311035-s3tkbh9r 153 62 to to IN cord-311035-s3tkbh9r 153 63 SARS SARS NNP cord-311035-s3tkbh9r 153 64 - - HYPH cord-311035-s3tkbh9r 153 65 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 153 66 spike spike NN cord-311035-s3tkbh9r 153 67 protein protein NN cord-311035-s3tkbh9r 154 1 prevents prevent VBZ cord-311035-s3tkbh9r 154 2 rapid rapid JJ cord-311035-s3tkbh9r 154 3 mutational mutational JJ cord-311035-s3tkbh9r 154 4 escape escape NN cord-311035-s3tkbh9r 154 5 seen see VBN cord-311035-s3tkbh9r 154 6 with with IN cord-311035-s3tkbh9r 154 7 individual individual JJ cord-311035-s3tkbh9r 154 8 antibodies antibody NNS cord-311035-s3tkbh9r 155 1 SARS SARS NNP cord-311035-s3tkbh9r 155 2 - - HYPH cord-311035-s3tkbh9r 155 3 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 155 4 spike spike NN cord-311035-s3tkbh9r 155 5 is be VBZ cord-311035-s3tkbh9r 155 6 able able JJ cord-311035-s3tkbh9r 155 7 to to TO cord-311035-s3tkbh9r 155 8 rapidly rapidly RB cord-311035-s3tkbh9r 155 9 acquire acquire VB cord-311035-s3tkbh9r 155 10 mutations mutation NNS cord-311035-s3tkbh9r 155 11 to to TO cord-311035-s3tkbh9r 155 12 escape escape VB cord-311035-s3tkbh9r 155 13 neutralizing neutralize VBG cord-311035-s3tkbh9r 155 14 monoclonal monoclonal JJ cord-311035-s3tkbh9r 155 15 antibodies antibody NNS cord-311035-s3tkbh9r 155 16 in in IN cord-311035-s3tkbh9r 155 17 tissue tissue NN cord-311035-s3tkbh9r 155 18 culture culture NN cord-311035-s3tkbh9r 155 19 , , , cord-311035-s3tkbh9r 155 20 necessitating necessitate VBG cord-311035-s3tkbh9r 155 21 the the DT cord-311035-s3tkbh9r 155 22 combination combination NN cord-311035-s3tkbh9r 155 23 of of IN cord-311035-s3tkbh9r 155 24 multiple multiple JJ cord-311035-s3tkbh9r 155 25 non non JJ cord-311035-s3tkbh9r 155 26 - - JJ cord-311035-s3tkbh9r 155 27 competing competing JJ cord-311035-s3tkbh9r 155 28 monoclonals monoclonal NNS cord-311035-s3tkbh9r 155 29 in in IN cord-311035-s3tkbh9r 155 30 a a DT cord-311035-s3tkbh9r 155 31 cocktail cocktail NN cord-311035-s3tkbh9r 155 32 to to TO cord-311035-s3tkbh9r 155 33 prevent prevent VB cord-311035-s3tkbh9r 155 34 resistance resistance NN cord-311035-s3tkbh9r 155 35 Structural structural JJ cord-311035-s3tkbh9r 155 36 basis basis NN cord-311035-s3tkbh9r 155 37 for for IN cord-311035-s3tkbh9r 155 38 the the DT cord-311035-s3tkbh9r 155 39 recognition recognition NN cord-311035-s3tkbh9r 155 40 of of IN cord-311035-s3tkbh9r 155 41 the the DT cord-311035-s3tkbh9r 155 42 SARS SARS NNP cord-311035-s3tkbh9r 155 43 - - HYPH cord-311035-s3tkbh9r 155 44 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 155 45 by by IN cord-311035-s3tkbh9r 155 46 full full JJ cord-311035-s3tkbh9r 155 47 - - HYPH cord-311035-s3tkbh9r 155 48 length length NN cord-311035-s3tkbh9r 155 49 human human JJ cord-311035-s3tkbh9r 155 50 ACE2 ACE2 NNP cord-311035-s3tkbh9r 155 51 Structure Structure NNP cord-311035-s3tkbh9r 155 52 of of IN cord-311035-s3tkbh9r 155 53 SARS SARS NNP cord-311035-s3tkbh9r 155 54 coronavirus coronavirus NN cord-311035-s3tkbh9r 155 55 spike spike NN cord-311035-s3tkbh9r 155 56 receptor receptor NN cord-311035-s3tkbh9r 155 57 - - HYPH cord-311035-s3tkbh9r 155 58 binding bind VBG cord-311035-s3tkbh9r 155 59 domain domain NN cord-311035-s3tkbh9r 155 60 complexed complexe VBN cord-311035-s3tkbh9r 155 61 with with IN cord-311035-s3tkbh9r 155 62 receptor receptor NN cord-311035-s3tkbh9r 155 63 An an DT cord-311035-s3tkbh9r 155 64 improved improved JJ cord-311035-s3tkbh9r 155 65 platform platform NN cord-311035-s3tkbh9r 155 66 for for IN cord-311035-s3tkbh9r 155 67 functional functional JJ cord-311035-s3tkbh9r 155 68 assessment assessment NN cord-311035-s3tkbh9r 155 69 of of IN cord-311035-s3tkbh9r 155 70 large large JJ cord-311035-s3tkbh9r 155 71 protein protein NN cord-311035-s3tkbh9r 155 72 libraries library NNS cord-311035-s3tkbh9r 155 73 in in IN cord-311035-s3tkbh9r 155 74 mammalian mammalian JJ cord-311035-s3tkbh9r 155 75 cells cell NNS cord-311035-s3tkbh9r 155 76 Mammalian mammalian JJ cord-311035-s3tkbh9r 155 77 cell cell NN cord-311035-s3tkbh9r 155 78 surface surface NN cord-311035-s3tkbh9r 155 79 display display NN cord-311035-s3tkbh9r 155 80 for for IN cord-311035-s3tkbh9r 155 81 monoclonal monoclonal JJ cord-311035-s3tkbh9r 155 82 antibody antibody NN cord-311035-s3tkbh9r 155 83 - - HYPH cord-311035-s3tkbh9r 155 84 based base VBN cord-311035-s3tkbh9r 155 85 FACS FACS NNP cord-311035-s3tkbh9r 155 86 selection selection NN cord-311035-s3tkbh9r 155 87 of of IN cord-311035-s3tkbh9r 155 88 viral viral JJ cord-311035-s3tkbh9r 155 89 envelope envelope NN cord-311035-s3tkbh9r 155 90 proteins protein NNS cord-311035-s3tkbh9r 155 91 HIV HIV NNP cord-311035-s3tkbh9r 155 92 vaccine vaccine NN cord-311035-s3tkbh9r 155 93 design design NN cord-311035-s3tkbh9r 155 94 to to TO cord-311035-s3tkbh9r 155 95 target target VB cord-311035-s3tkbh9r 155 96 germline germline JJ cord-311035-s3tkbh9r 155 97 precursors precursor NNS cord-311035-s3tkbh9r 155 98 of of IN cord-311035-s3tkbh9r 155 99 glycan glycan NN cord-311035-s3tkbh9r 155 100 - - HYPH cord-311035-s3tkbh9r 155 101 dependent dependent JJ cord-311035-s3tkbh9r 155 102 broadly broadly RB cord-311035-s3tkbh9r 155 103 neutralizing neutralize VBG cord-311035-s3tkbh9r 155 104 antibodies antibody NNS cord-311035-s3tkbh9r 155 105 Structure structure NN cord-311035-s3tkbh9r 155 106 - - HYPH cord-311035-s3tkbh9r 155 107 based base VBN cord-311035-s3tkbh9r 155 108 design design NN cord-311035-s3tkbh9r 155 109 of of IN cord-311035-s3tkbh9r 155 110 native native JJ cord-311035-s3tkbh9r 155 111 - - HYPH cord-311035-s3tkbh9r 155 112 like like JJ cord-311035-s3tkbh9r 155 113 HIV-1 HIV-1 NNP cord-311035-s3tkbh9r 155 114 envelope envelope NN cord-311035-s3tkbh9r 155 115 trimers trimer NNS cord-311035-s3tkbh9r 155 116 to to TO cord-311035-s3tkbh9r 155 117 silence silence VB cord-311035-s3tkbh9r 155 118 non non JJ cord-311035-s3tkbh9r 155 119 - - JJ cord-311035-s3tkbh9r 155 120 neutralizing neutralize VBG cord-311035-s3tkbh9r 155 121 epitopes epitope NNS cord-311035-s3tkbh9r 155 122 and and CC cord-311035-s3tkbh9r 155 123 eliminate eliminate VB cord-311035-s3tkbh9r 155 124 CD4 CD4 NNP cord-311035-s3tkbh9r 155 125 binding bind VBG cord-311035-s3tkbh9r 155 126 Structural structural JJ cord-311035-s3tkbh9r 155 127 architecture architecture NN cord-311035-s3tkbh9r 155 128 of of IN cord-311035-s3tkbh9r 155 129 a a DT cord-311035-s3tkbh9r 155 130 dimeric dimeric JJ cord-311035-s3tkbh9r 155 131 class class NN cord-311035-s3tkbh9r 155 132 C c NN cord-311035-s3tkbh9r 155 133 GPCR GPCR NNP cord-311035-s3tkbh9r 155 134 based base VBN cord-311035-s3tkbh9r 155 135 on on IN cord-311035-s3tkbh9r 155 136 co co NN cord-311035-s3tkbh9r 155 137 - - NN cord-311035-s3tkbh9r 155 138 trafficking trafficking NN cord-311035-s3tkbh9r 155 139 of of IN cord-311035-s3tkbh9r 155 140 sweet sweet JJ cord-311035-s3tkbh9r 155 141 taste taste NN cord-311035-s3tkbh9r 155 142 receptor receptor NN cord-311035-s3tkbh9r 155 143 subunits subunit NNS cord-311035-s3tkbh9r 155 144 Enrich enrich VB cord-311035-s3tkbh9r 155 145 : : : cord-311035-s3tkbh9r 155 146 software software NN cord-311035-s3tkbh9r 155 147 for for IN cord-311035-s3tkbh9r 155 148 analysis analysis NN cord-311035-s3tkbh9r 155 149 of of IN cord-311035-s3tkbh9r 155 150 protein protein NN cord-311035-s3tkbh9r 155 151 function function NN cord-311035-s3tkbh9r 155 152 by by IN cord-311035-s3tkbh9r 155 153 enrichment enrichment NN cord-311035-s3tkbh9r 155 154 and and CC cord-311035-s3tkbh9r 155 155 depletion depletion NN cord-311035-s3tkbh9r 155 156 of of IN cord-311035-s3tkbh9r 155 157 variants variant NNS cord-311035-s3tkbh9r 155 158 HIV-1 HIV-1 NNP cord-311035-s3tkbh9r 155 159 broadly broadly RB cord-311035-s3tkbh9r 155 160 neutralizing neutralize VBG cord-311035-s3tkbh9r 155 161 antibody antibody NN cord-311035-s3tkbh9r 155 162 precursor precursor NN cord-311035-s3tkbh9r 155 163 B b NN cord-311035-s3tkbh9r 155 164 cells cell NNS cord-311035-s3tkbh9r 155 165 revealed reveal VBN cord-311035-s3tkbh9r 155 166 by by IN cord-311035-s3tkbh9r 155 167 germline germline NN cord-311035-s3tkbh9r 155 168 - - HYPH cord-311035-s3tkbh9r 155 169 targeting target VBG cord-311035-s3tkbh9r 155 170 immunogen immunogen NN cord-311035-s3tkbh9r 155 171 Isolating Isolating NNP cord-311035-s3tkbh9r 155 172 and and CC cord-311035-s3tkbh9r 155 173 engineering engineer VBG cord-311035-s3tkbh9r 155 174 human human JJ cord-311035-s3tkbh9r 155 175 antibodies antibody NNS cord-311035-s3tkbh9r 155 176 using use VBG cord-311035-s3tkbh9r 155 177 yeast yeast NN cord-311035-s3tkbh9r 155 178 surface surface NN cord-311035-s3tkbh9r 155 179 display display VB cord-311035-s3tkbh9r 155 180 The the DT cord-311035-s3tkbh9r 155 181 humanization humanization NN cord-311035-s3tkbh9r 155 182 of of IN cord-311035-s3tkbh9r 155 183 N n NN cord-311035-s3tkbh9r 155 184 - - HYPH cord-311035-s3tkbh9r 155 185 glycosylation glycosylation NN cord-311035-s3tkbh9r 155 186 pathways pathway NNS cord-311035-s3tkbh9r 155 187 in in IN cord-311035-s3tkbh9r 155 188 yeast yeast NN cord-311035-s3tkbh9r 155 189 Glycan Glycan NNP cord-311035-s3tkbh9r 155 190 - - HYPH cord-311035-s3tkbh9r 155 191 dependent dependent JJ cord-311035-s3tkbh9r 155 192 neutralizing neutralize VBG cord-311035-s3tkbh9r 155 193 antibodies antibody NNS cord-311035-s3tkbh9r 155 194 are be VBP cord-311035-s3tkbh9r 155 195 frequently frequently RB cord-311035-s3tkbh9r 155 196 elicited elicit VBN cord-311035-s3tkbh9r 155 197 in in IN cord-311035-s3tkbh9r 155 198 individuals individual NNS cord-311035-s3tkbh9r 155 199 chronically chronically RB cord-311035-s3tkbh9r 155 200 infected infect VBN cord-311035-s3tkbh9r 155 201 with with IN cord-311035-s3tkbh9r 155 202 HIV-1 HIV-1 NNP cord-311035-s3tkbh9r 155 203 Clade Clade NNP cord-311035-s3tkbh9r 155 204 B B NNP cord-311035-s3tkbh9r 155 205 or or CC cord-311035-s3tkbh9r 155 206 C. C. NNP cord-311035-s3tkbh9r 155 207 AIDS AIDS NNP cord-311035-s3tkbh9r 155 208 Research Research NNP cord-311035-s3tkbh9r 155 209 and and CC cord-311035-s3tkbh9r 155 210 Human Human NNP cord-311035-s3tkbh9r 155 211 Retroviruses Retroviruses NNPS cord-311035-s3tkbh9r 155 212 Exceptional exceptional JJ cord-311035-s3tkbh9r 155 213 diversity diversity NN cord-311035-s3tkbh9r 155 214 and and CC cord-311035-s3tkbh9r 155 215 selection selection NN cord-311035-s3tkbh9r 155 216 pressure pressure NN cord-311035-s3tkbh9r 155 217 on on IN cord-311035-s3tkbh9r 155 218 SARS SARS NNP cord-311035-s3tkbh9r 155 219 - - HYPH cord-311035-s3tkbh9r 155 220 CoV CoV NNP cord-311035-s3tkbh9r 155 221 and and CC cord-311035-s3tkbh9r 155 222 SARS SARS NNP cord-311035-s3tkbh9r 155 223 - - HYPH cord-311035-s3tkbh9r 155 224 CoV-2 CoV-2 NNP cord-311035-s3tkbh9r 155 225 host host NN cord-311035-s3tkbh9r 155 226 receptor receptor NN cord-311035-s3tkbh9r 155 227 in in IN cord-311035-s3tkbh9r 155 228 bats bat NNS cord-311035-s3tkbh9r 155 229 compared compare VBN cord-311035-s3tkbh9r 155 230 to to IN cord-311035-s3tkbh9r 155 231 other other JJ cord-311035-s3tkbh9r 155 232 mammals mammal NNS cord-311035-s3tkbh9r 155 233 Structural structural JJ cord-311035-s3tkbh9r 155 234 basis basis NN cord-311035-s3tkbh9r 155 235 of of IN cord-311035-s3tkbh9r 155 236 receptor receptor NN cord-311035-s3tkbh9r 155 237 recognition recognition NN cord-311035-s3tkbh9r 155 238 by by IN cord-311035-s3tkbh9r 155 239 SARS SARS NNP cord-311035-s3tkbh9r 155 240 - - HYPH cord-311035-s3tkbh9r 155 241 CoV-2 CoV-2 NNP