id author title date pages extension mime words sentences flesch summary cache txt cord-286001-pu1fetq7 Zang, Ruochen TMPRSS2 and TMPRSS4 mediate SARS-CoV-2 infection of human small intestinal enterocytes 2020-04-23 .txt text/plain 2049 145 50 In addition to TMPRSS2, another mucosa-specific serine protease, TMPRSS4, also enhanced SARS-CoV-2 spike fusogenic activity and mediated viral entry into host cells. Importantly, we found that 160 expression of TMPRSS4 but not ST14 also resulted in a significant increase in the levels of viral RNA and infectious virus titers in the presence of ACE2 ( Fig. 3B and S3C) . Collectively, we have shown that TMPRSS2 and TMPRSS4 activate SARS-CoV-2 S and 187 enhance membrane fusion and viral endocytosis into host cells. Importantly, abrogating TMPRSS4 expression led 209 to a 4-fold reduction in SARS-CoV-2 chimera virus replication in human enteroid, even 210 more significant than TMPRSS2 knockout (Fig. 4B) , highlighting its importance in 211 mediating virus replication in primary cells. It is possible that in the 293 small intestine, whereas SARS-CoV-2 is relatively stable, additional proteases such as 294 trypsin likely enhance viral pathogenesis by triggering more robust IEC fusion (Fig. S2A) . ./cache/cord-286001-pu1fetq7.txt ./txt/cord-286001-pu1fetq7.txt