cord-008613-tysyq6o4	1988	Simian virus 5 (SV5), a prototype paramyxovirus, has a single-stranded, negative sense genomic RNA (vRNA) approximately 15,000 nucleotides in chain length that is transcribed in infected cells by the virion-associated RNA transcriptase to yield virus-specific mRNAs. The SV5 "P" gene has been shown to encode both the P protein (Mr = 44,000), and protein V (Mr = 24,000) by the arrest of translation in vitro of both P and V using a cDNA clone derived from SV5-specific mRNAs (Paterson et al., 1984) . Antigenic Region Mapping of the P and V Monoclonal Antibodies on the P and V Gene Using T7 RNA Polymerase Runoff Transcripts, In Vitro Translation, and Immunoprecipitation The full-length P203-1 DNA insert cloned using Xbal linkers (XX) and a Hindlll to Xbal fragment (HX) containing the 3'' two-thirds of the P203-1 DNA were placed under the control of the T7 promoter in the plasmid pGEM-2.
cord-252433-0e9lonq4	2009	As a result, HIV-1 mutants lacking a functional rev gene are able to express the proteins encoded by fully spliced viral mRNAs, that is, Tat, Nef, and the defective Rev protein itself, but cannot express any of the proteins encoded by incompletely spliced viral mRNAs, including Gag, Pol, and Env. The transcripts encoding these viral structural proteins, however, can be detected in the nucleus of cells infected by Rev-deficient viruses, where they are either degraded or eventually fully spliced and then exported (Cullen, 2003) . MPMV has a simpler genomic organization than HIV-1 and only encodes the three structural proteins Picornaviruses and some flaviviruses Recruits cellular translation factors and ribosomal subunits to viral translation initiation codons in the absence of an mRNA cap Gag, Pol, and Env. Nevertheless, MPMV expresses both a genome-length Gag/ Pol mRNA and a spliced Env mRNA.
cord-253259-hmn7mg8j	1993	Abstract Three-dimensional structures of a native simian and reassortant rotavirus have been determined by electron cryomicroscopy and computer image processing. The structural features of the native virus confirm that the hemagglutinin spike is a dimer of VP4, substantiated by in vivo radiolabeling studies. The difference map between the two structures reveals a novel large globular domain of VP4 buried within the virion that interacts extensively with the intermediate shell protein, VP6. Our results suggest that assembly of VP4 precedes that of VP7, the major outer shell protein, and that VP4 may play an important role in the receptor recognition and budding process through the rough endoplasmic reticulum during virus maturation. Figure 3A shows a surface representation of the The reconstructed density map of SAI 1-4F reveals the complex organization of the outer shell of rotavirus.
cord-253302-keh7s758	2019	Our atomic models of the portal and capsid/CATC, together with visualization of CATCs'' variable occupancy and alternate orientation of CATC-interacting vertex triplexes, suggest a mechanism whereby the portal orchestrates procapsid formation and asymmetric long-range determination of CATC attachment during DNA packaging prior to pleomorphic tegumentation/envelopment. Unlike the comparatively high occupancies of capsid-associated tegument proteins in alphaherpesviruses Wang et al., 2018) and betaherpesviruses Yu et al., 2017) , KSHV CATC binding sites are markedly partially and/or more flexibly occupied, leading to poorly resolved CATC structures in prior icosahedral reconstructions of KSHV (Dai et al., 2014 . Thus, to accurately assess the specific occupancy of penton vertex CATCs and to understand the structural basis of a CATC''s discriminatory association with portal and penton vertices, we relaxed 5-fold symmetry for penton vertex sub-particles and performed 3D focused classification of their CATC-binding registers ( Figure S1 ).
cord-255856-0xqllbzz	1985	A specific size class of O-linked oligosaccharides, recovered following mild alkaline hydrolysis and reduction of ZP3, is shown to possess sperm receptor activity and to bind to sperm. In these experiments, a competition assay (Bleil and Wassarman, 1980a; Florman et al., 1984) was used to determine the ability of oligosaccharides, derived from either solubilized zonae pellucidae or purified zona pellucida glycoproteins, to inhibit the binding of sperm to eggs in vitro ("sperm receptor activity"). On the other hand, egg zonae pellucidae subjected to mild alkaline hydrolysis, under the conditions described above, lost approximately 90% of the sperm receptor activity present in untreated samples and in samples treated only with distilled water (Figure 2) . Initial experiments demonstrated that radiolabeled (3H-NaBH,) oligosaccharides, possessing sperm receptor activity, could be recovered from alkaline hydrolysates of egg zonae pellucidae.
cord-256156-mywhe6w9	2020	We show that SARS-CoV-2 spike protein interacts with both cellular heparan sulfate and angiotensin converting enzyme 2 (ACE2) through its Receptor Binding Domain (RBD). Unfractionated heparin, non-anticoagulant heparin, heparin lyases, and lung heparan sulfate potently block spike protein binding and/or infection by pseudotyped virus and authentic SARS-CoV-2 virus. In this report, we show that the ectodomain of the SARS-CoV-2 spike (S) protein interacts with cell surface HS through the Receptor Binding Domain (RBD) in the S1 subunit. Adjacent to the ACE2 binding site and exposed in the RBD lies a group of positively-charged amino acid residues that represents a potential site that could interact with heparin or heparan sulfate ( Fig. 1A and Suppl. The SARS-CoV-2 spike protein depends on cellular heparan sulfate for cell binding. Heparin inhibits cellular invasion by SARS-CoV-2: structural dependence of the interaction of the surface protein (spike) S1 receptor binding domain with heparin
cord-258372-w0j0n8mn	2020	Shoring up the foundation of academic science will require a concerted effort between funding agencies, universities, and the public to rethink how we support scientists, with a special emphasis on early career researchers. Shoring up the foundation of academic science will require a concerted effort between funding agencies, universities, and the public to rethink how we support scientists, with a special emphasis on early career researchers. Women, parents, and individuals who identify as racial or ethnic minorities leave science, technology, engineering, and math (STEM) fields as early career researchers at an excessively high rate in the best of times and will undoubtedly suffer more from the present lab closures. Ensuring a Durable Future for Academic Science Post-COVID19 Recovery from the immediate COVID19 crisis necessitates a multi-pronged approach including fiscal and non-fiscal strategies to help graduate students, postdoctoral fellows, and early and later career faculty.
cord-259681-k9cnikqk	1983	These studies were carried out not only under conditions designed to allow normal glycoprotein processing, but also in the presence of monensin, an ionophore known to cause accumulation of secreted and membrane proteins and virions in Golgi-derived vacuoles (Tartakoff and Vassalli, 1978; Uchida et al., 1979; Johnson and Schlesinger, 1980; Johnson and Spear, 1982) , and in ricin-resistant cells defective in the processing of N-linked oligosaccharides. Our results indicate that extension of O-linked oligosaccharides to yield chains of sufficient number or size to affect electrophoretic mobilities of the glycoproteins, and probably also addition of the first amino acid-linked GalNAc residues, occur in the Golgi apparatus subsequent to addition of fatty acid and coincident with the processing of high-mannose-type Nlinked oligosaccharides to complex-type oligosaccharides. The "C-labeled HSVl glycoproteins gC and gD were isolated on preparative SDS-polyacrylamide gels and treated with 0.05 M NaOH, 1 M NaBHa at 45°C for 14-20 hr (mild alkaline borohydride), conditions shown to selectively release O-linked oligosaccharides (Spiro, 1966; Marshall and Neuberger, 1977) .
cord-263468-996kl9jz	1988	Abstract We assessed the alterations of viral gene expression occurring during persistent infections by cloning full-length transcripts of measles virus (MV) genes from brain autopsies of two subacute sclerosing panencephalitis patients and one measles inclusion body encephalitis (MIBE) patient. One of these nucleotide substitutions and one deletion resulted in alteration of the reading frames of two fusion genes, as confirmed by in vitro translation of synthetic mRNAs. One cluster of mutations was exceptional; in the matrix gene of the MIBE case, 50% of the U residues were changed to C, which might result from a highly biased copying event exclusively affecting this gene. most likely based on one hand on the low fidelity of RNA To assess the variability in strains of lytic viruses, and replication (Domingo et al., 1978; for review see Steinto estimate the number of mutations introduced during hauer and Holland, 1987) and on the other hand on the persistence, we counted the differences of lytic and perlow selective pressure exerted on viral genomes in nonsistent viruses from a consensus as defined above.
cord-266480-u8o4eitu	2020	Operation Outbreak (OO) is an educational curriculum and simulation platform that uses Bluetooth to spread a virtual "pathogen" in real-time across smartphones in close proximity. The app-generated data from these simulations represented the "ground truth" of the mock outbreaks, captured several essential features of SARS-CoV-2, and allowed us to observe behavioral changes among participants--many of which are now being mirrored in real life. Our 2018 SMA Ebola simulation first showed how student social-distancing could affect an "outbreak''s" trajectory ( Figure 2A More detailed data from the 2019 simulation allowed us to reconstruct transmission chains over time and identify important features of the outbreak, such as the existence of two super-spreaders causing 4 and 5 secondary infections early in the game ( Figure 2C ). We envision OO as playing two key roles: (1) as a pedagogical platform for teaching fundamentals of pandemic response that are vital for the public to understand and (2) as a novel system for simulating outbreaks and evaluating real-world mitigation strategies, including those needed to restart in-person education.
cord-267046-ewnjgps5	2001	key: cord-267046-ewnjgps5 title: Virus Evolution: How Does an Enveloped Virus Make a Regular Structure? cord_uid: ewnjgps5 They propose a fit of E1 into the cryo-75 residues long, of which about 38 residues are present EM density of Semliki Forest virus determined to 9 Å in the ectodomain. The paper by Pletnev ture flavivirion containing prM (about 170 residues) et al. The Evolution of Enveloped Viruses E2 projects upward to the full-length of the spike. Thus, The parallels between the assembly of alphaviruses and E1 forms what has been called the skirt that surrounds flaviviruses and the similarities in structure revealed by the lipid bilayer and part of the lower domains of the the present studies suggest that an enveloped virus spikes, whereas E2 forms the projecting part of the with an icosahedral structure arose long ago and has spike. viruses whose structures are more or less known use quite different assembly mechanisms ( Virus evolution
cord-269023-g21a9ik2	2020	When he transferred these active lymphocytes-later found to be B cells-from an antigen-exposed animal to a naive animal (an ingeniously simple experiment), Gowans found that he could transfer antibody-mediated immunity as well. In a paper published in Nature, Michel Nussenzweig and his colleagues dissected the immune response to SARS-CoV-2 infection (Robbiani et al., 2020) . The sustained activation of certain patterns of chemokines and cytokines was correlated with severe illness-a phenomenon that Iwasaki has termed ''''immunological misfiring.'''' A more recent paper, published in Cell, also implicated dysfunctions in innate immune cells, particularly myeloid cells such as neutrophils and monocytes, in patients with severe COVID infection (Schulte-Schrepping et al., 2020) . ''''If you mount a robust innate immune response during the early phase of infection, you control the virus and have a mild disease.
cord-270082-byxd4o4m	1993	Readthrough Assay and Secondary Screen of the ctf Collection When transcription from a strong promoter is initiated toward a CEN DNA sequence, the mitotic segregational function of the centromere is destroyed (Hill and Bloom, 1987) without disruption of its 180-220 bp nuclease protected region (Bloom et al., 1984; Hill and Bloom, 1987) , indicating that at least some of the kinetochore complex remains intact. To test the hypothesis that a CfN DNA-protein complex was responsible for the transcriptional block, we replaced the wild-type CENG sequence with a CEN6 sequence containing a single-nucleotide point mutation (CDEIII-15C) in the central element of the palindrome of CDEIII (CCG). Of 34 cff mutants screened (see Experimental Procedures for list), 7 were identified as putative kinetochore mutants because they produced an intermediate level of blue colony color between the levels of the CTF+ strains carrying the wild-type and mutant CEN reporters.
cord-271032-imc6woht	2020	
cord-272520-7mci4mip	1995	To mediate budding of infectious viral particles through intracellular membranes, viral glycoproteins must fulfill two requirements: a signal for sorting to an intracellular compartment and an interaction with the core proteins of the virus. Similar to certain classic oncoviruses, the foamy viruses utilize a B/D-type virus assembly strategy by which immature viral capsids assemble in the cytoplasm in advance of virion budding (Achong et al., 1971; Hooks and Gibbs, 1975) . We hypothesized that foamy virus glycoproteins must possess a specific signal for sorting to an intracellular compartment of the secretory pathway. Remarkably, we identified the dilysine ER retrieval signal at the cytoplasmic carboxyl termini of four of the five available foamy virus glycoprotein sequences ( Table 2 ). If the glycoprotein cytoplasmic tails interact with preassembled viral capsids, which may localize to the same intracellular site, coordinated budding of glycoprotein-bearing infectious virus particles into an early post-ER compartment results.
cord-279463-bli8hwda	1986	As type II membrane proteins contain only a single stretch of hydrophobic amino acid residues, this might function as a signal for membrane insertion as well as a membrane anchor (Markoff et al., 1984; Spiess and Lodish, 1986) . plycat is an in-frame fusion between the 5'' region of ly encoding the cytoplas, mic, membrane-spanning segment plus 12 amino acids of the exoplasmic portion of ly and the gene encoding the cytoplasmic protein chloramphenicol acetyltransferase (CAT). After protease digestion in the presence of microsomal membranes, lyCAT* is reduced in molecular weight by about 2 kd, suggesting that it exposes 20-30 amino acid residues on the cytoplasmic side ( Figure 3 , lanes 2 and 3). This signal sequence is located in the amino-terminal half of the membrane-spanning segment, and it is cleaved when the preceding cytoplasmic domain is removed.
cord-284609-1q75zw6b	1982	
cord-284944-hcgfe9wv	2020	Thus, we performed high dimensional flow cytometry and single cell RNA sequencing of COVID-19 patient peripheral blood cells and detected the disappearance of non-classical CD14LowCD16High monocytes, the accumulation of HLA-DRLow classical monocytes, and the release of massive amounts of calprotectin (S100A8/S100A9) in severe cases. Validating these discovery experiments, we performed mass cytometry analysis of an independent cohort of 12 patients (four in each group; control, mild and severe) ( Table S5) , which showed a lower fraction of CD14 Low CD16 High non-classical monocytes in severe compared to mild patients ( Figure 3F and 3G ). This study presents evidence that patients who develop a severe COVID-19 exhibit high levels of calprotectin and inflammatory cytokines and chemokines correlating with an emergency myelopoiesis generating ROS-and NOS-expressing immunosuppressive myeloid cells (HLA-DR Low monocytes and immature subsets of neutrophils).
cord-287349-1zcq7kzx	2020	title: Structural basis for helicase-polymerase coupling in the SARS-CoV-2 replication-transcription complex Here we present cryo-electron microscopic structures of the SARS-CoV-2 holo-RdRp with an RNA template-product in complex with two molecules of the nsp13 helicase. The structure places the nucleic acid-binding ATPase domains of the helicase directly in front of the replicating-transcribing holo-RdRp, constraining models for nsp13 function. The analogous structural 234 arrangement leads us to propose that the SARS-CoV-2 RdRp may backtrack, generating a single-235 stranded RNA segment at the 3''-end that would extrude out the RdRp secondary channel 236 Table S1 ; Video S1). This aspect of helicase function could provide the NTP-296 dependent motor activity necessary to backtrack the RdRp. In cellular organisms, DdRp 297 backtracking plays important roles in many processes, including the control of pausing during 298 transcription elongation, termination, DNA repair, and fidelity (Nudler, 2012) . Structural Basis for RNA Replication by the SARS-CoV-2 Polymerase
cord-287815-alv30uk5	1992	As we have seen, there are three key elements underlying our general view of the Golgi: that the Golgi consists of several discrete compartments (cis, medial, trans, and TGN) corresponding to individual or groups of cisternae; that transit between these compartments occurs viavesicular carriers; and that the transport process is inherently nonselective with respect to the passenger proteins. While distinct from the CGN or TGN, we assume that the medial cisternae represent a single functionally continuous compartment, irrespective of the actual number of physically separate cisternal elements in any one Golgi complex. Given that VSV G protein in early Golgi compartments was transported with the highest efficiency (Fries and Rothman, 1981) the transport event assayed was postulated to reflect the formation of vesicles from cis (early) cisternae and the fusion of these vesicles with medial cisternae (which contain the GlcNAc transferase) (Rothman and Orci, 1990) (Figure 4) .
cord-289765-79cmcvfi	2020	
cord-291790-z5rwznmv	2020	
cord-294429-isivkz8b	2020	
cord-295062-8rl4kswe	2006	Virus Particles as Devices for Targeted Gene Transfer A viral particle is composed of nucleic acids (RNA or DNA), protein, and, in the case of enveloped viruses, membrane lipids. Viruses use signaling activities to induce changes in the cell that promote viral entry and early cytoplasmic events, as well as to optimize later processes in the replication cycle. Like cholera toxin, these viruses bind to the sugar moiety of gangliosides and enter cells via caveolar/raft pathways that are dependent on cholesterol ( Figures 2D and 2E ) and the activation of tyrosine-kinase signaling cascades (Anderson et al., 1996; Pelkmans et al., 2001; Smith et al., 2003a; Stang et al., 1997; Tsai et al., 2003) . Nevertheless, in the majority of cases, the transfer of viral genomes from cell to cell appears to occur through the formation of virus particles that are released from infected cells and use the mechanisms described above to enter new uninfected hosts.
cord-295894-us5x1jtg	2020	Abbreviations: FABPs, fatty acid binding proteins; NFκB: nuclear factor kappa B; COX2, cyclooxygenase-2; CER, ceramide; LXR, liver X receptor; PGE2, prostaglandin E2; SCD1, stearoyl-CoA desaturase 1; STAT, signal transducer and activator of transcription; LTA4, leukotriene A4; RAR, retinoic acid receptor; NLRP3, nucleotide-binding domain leucine-rich repeat and pyrin domain containing 3; ASC, apoptosis-associated speck-like protein containing a caspase-recruitment domain; IFNβ, interferon β; LTB4, leukotriene B4; HSL, hormone sensitive lipase; PPAR, peroxisome proliferator-activated receptors; DIO2, deiodinase type 2; β-AR, β-adrenergic receptor; ALDH1, aldehyde dehydrogenase isoform 1; PCK1, phosphoenolpyruvate carboxykinase 1. Generally, FABPs function as cytoplasmic lipid chaperones to (1) facilitate fatty acid solubilization, trafficking, and metabolism; (2) interact with various membrane and intracellular proteins (e.g., peroxisome proliferator-activated receptors [PPARs] , hormone sensitive lipase [HSL]); and (3) regulate tissue and cellular specific lipid responses (middle wheel panel). In summary, accumulating evidence has demonstrated that FABP members not only exert overlapping functions in lipid binding and transport but exhibit unique characteristics in specific cells and tissues as well. Expression of Adipocyte/Macrophage Fatty Acid-Binding Protein in Tumor-Associated Macrophages Promotes Breast Cancer Progression
cord-301997-63160t7f	1987	
cord-302020-ypsh3rjv	2020	In addition to the canonical genomic and 9 subgenomic RNAs, SARS-CoV-2 produces transcripts encoding unknown ORFs with fusion, deletion, and/or frameshift. Functional investigation of the unknown transcripts and RNA modifications discovered in this study will open new directions to our understanding of the life cycle and pathogenicity of SARS-CoV-2. (A) Read counts from nanopore direct RNA sequencing of total RNA from Vero cells infected with SARS-CoV-2. We further discovered RNA modification sites and measured the poly(A) tail length of gRNAs and sgRNAs. To delineate the SARS-CoV-2 transcriptome, we first performed DRS runs on a MinION nanopore sequencer with total RNA extracted from Vero cells infected with SARS-CoV-2 (Be-taCoV/Korea/KCDC03/2020). To unambiguously investigate the modifications, we generated negative control RNAs by in vitro transcription of the viral sequences and performed a DRS run on these unmodified controls ( Figure S4A ).
cord-305173-95o5z685	2008	In the complex inflammatory response initiated by HCl in the lungs, one might expect that TLR4 would be activated by several different endogenous stimuli; however, mice lacking TLR4, TRIF, or TRAF6 all resisted HClas well as OxPAPC-induced inflammation, supporting a role for OxPAPC as an important stimulus of TLR4 activation in this model. As in the HCl injury model, immunohistochemical analysis identified OxPAPC in the lungs, but mice lacking TLR4 or TRIF had lung inflammation that was much less severe. Mice lacking the Ncf1 protein, which lack an active NADPH oxidase complex, were protected from viral lung inflammation and did not form OxPAPC in the airspaces, further supporting a key role for oxidation of phospholipids in the pathogenic pathway. OxPAPC activates TLR4 expressed by myeloid cells (an alveolar macrophage is shown), and the intracellular signal is transduced by the adaptor proteins TRIF and TRAF6, leading to interleukin 6 (IL-6) production, inflammation, and alveolar damage.
cord-305290-xnjwv0d7	1990	A single base change in the mouse mammary tumor virus (MMTV) gag-pro shift site, from the normal A AAA AAC to A AAA AAG, surprisingly leads from ~2% to 50% -1 frameshifting at this sequence (a 25-fold increase); and the lo-fold decrease between A AAA AAG and A AAA AAA affords an interesting glimpse at how the nuances of codon-anticodon interaction can govern the efficiency of this type of shifting. These results should be interpreted with caution, as all the higher eukaryotic frameshifting studies with altered sequences have been done with a reticulocyte lysate cell-free translation system; there are likely to be differences in the number of ribosomes loaded per message, and perhaps in the tRNA balance, from less specialized cells in vivo.
cord-307021-uppekume	1988	Pro-OmpA preincubated at 21°C with membrane vesicles lost competence for subsequent membrane translocation ( Figure 6 , lane 11) while preincubation in the presence of membranes and trigger factor, but without ATP and NADH (lane 12), stabilized the assembly-active precursor. SRP Stabilizes ProOmpA for Membrane Translocation Like trigger factor, canine SRP ha8 been shown to recognize presecretory proteins, although until now its activity has been assayed in the context of a polysome. Nikko1 does not inhibit the membrane assembly of proOmpA that has already formed a complex with trigger factor (Figure 9 , lane 3, no detergent; lane 4, detergent added), and thus has no effect on the membrane translocation "machinery" per se or on the protease protection assay. It is likely that other soluble proteins, such as those encoded by the secA and se& genes, would bind to our preparations of plasma membrane vesicles or, if added to the in vitro translocation in the absence (lane 2) or presence (lanes 3 and 4) of trigger factor (100 ng).
cord-312115-foy3dsq4	2020	In line with these data, we found that CD8 + T cells specific for cytomegalovirus (CMV) or Epstein-Barr virus (EBV) more commonly expressed CD38, but not HLA-DR, Ki-67, or PD-1, in patients with acute moderate or severe COVID-19 compared with convalescent individuals and healthy blood donors, indicating limited bystander activation and proliferation during the early phase of infection with SARS-CoV-2 ( Figure 2A , B and Figure S3C ). On the basis of these observations, we quantified functional SARS-CoV-2-specific memory T cell responses across five distinct cohorts, including healthy individuals who donated blood either before or during the pandemic, family members who shared a household with convalescent individuals and were exposed at the time of symptomatic disease, and individuals in the convalescent phase after mild or severe COVID-19. These donors exhibited robust memory T cell responses months after infection, even in the absence of detectable circulating antibodies specific for SARS-CoV-2, indicating a previously unanticipated degree of population-level immunity against COVID-19.
cord-318276-so5jooj0	1987	RNA was isolated from noninfected or infected cells and then hybridized to 32P-labeled probes isolated from the 5'' end region, upstream of the 11K coding sequences of cDNA clones 3, 8, and 9 (see Figure 2 ). To confirm this, and to identify the regions from which they are transcribed, the cDNA-derived probes used in the previous experiment were hybridized to cloned DNA restriction fragments representing the entire vaccinia virus genome ( Figure 4 ). %P-labeled DNA probes (~3, ~9, p9, pllK) derived from the 5'' region of the corresponding cDNA clones or from genomic DNA (see Figure 2 ) were hybridized lo RNA isolated from uninfected (HeLa) or infected (Early, Late) cells, or to tRNA immobilized on a nitrocellulose membrane. Total late RNA from infected cells protected fragments of 127 and 128 nucleotides of the genomic probe, consistent with the previous experiments, which demonstrated that the sequence complementarity between the genomic DNA and 11K mRNA ends just upstream of the 11K ATG codon.
cord-321308-rwxhdg8r	2020	While clinical and in vitro data suggest that D614G changes the virus phenotype, the impact of the mutation on transmission, disease, and vaccine and therapeutic development are largely unknown. Following the emergence of SARS-CoV-2 in China in late 2019, and the rapid expansion of the COVID-19 pandemic in 2020, questions about viral evolution have come tumbling after. They present compelling data that an amino acid change in the virus'' spike protein, D614G, emerged early during the pandemic, and viruses containing G614 are now dominant in many places around the world. In support of their hypothesis, the authors provided evidence that clinical samples from G614 infections have a higher levels of viral RNA, and produced higher titers in pseudoviruses from in vitro experiments; results that now seem to be corroborated by others [e.g. Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus Naturally mutated spike proteins of SARS-CoV-2 variants show differential levels of cell entry
cord-321868-xk4yuibj	1990	Our tRNA overproduction data suggest that a leucyl-tRNA, probably tRNALeu UAG, an unusual leucine isoacceptor that recognizes all six leucine codons, slips from CUU-Leu onto UUA-Leu (in the +1 reading frame) during a translational pause at the AGG-Arg codon induced by the low availability of tRNAArg CCU, encoded by a single-copy essential gene. In these systems, a simultaneous slippage of tRNAs in the A and P sites of the translating ribosome on the homopolymeric sequence results in a frameshift to the pro orpol reading frame and suppression of the gag frame termination codon. The 14 nucleotide frameshift site has a Gln residue (rather than His) following Gly. The amino acid sequence through the 14 nucleotide site confirms the Gln residue after Gly (data not shown), supporting the notion that translation shifts to the +l reading frame by peptidyl-tRNA slippage on the CUU-Leu codon.
cord-326916-bakwk4tm	2020	
cord-327349-rxb6zfoc	2020	Inherent perturbations on cell subsets (e.g. lymphoid and myeloid malignancies), or therapy-induced impact on immune states (e.g. immune checkpoint blockade) may provide opportunities to understand contributions of distinct immune compartments and key regulators of the anti-SARS-CoV-2 response. Herein, we aim to provide an overview of knowledge to-date of the clinical features of COVID-19 observed in cancer patients, as well as potential impact of cancer and anti-cancer interventions on the immune response to SARS-CoV-2. However, what has been critically missing in cohort and registry reports to date are data on 1) the true prevalence of SARS-CoV-2 infection in the cancer population, given population screening has not been widely implemented; and 2) the experience of those who remain well (uninfected, asymptomatic or subclinically affected), to determine the drivers of mortality and the absolute risks of severe adverse events within the cancer community as a whole. A longitudinal understanding of the degree to which the immunocompromised states of cancer patients impact infection, viral clearance, clinical course of COVID-19, and subsequent generation of long-term immunity is needed.
cord-328289-3h3kmjlz	2020	Another Parkinson''s disease patient with obesity, hypertension and diabetes, exhibited at autopsy, in addition to hypoxic-ischemic neuronal damage, microhemorrhages, white matter lesions and enlarged perivascular spaces, but no evidence of SARS-CoV-2 in the brain (Kantonen et al., 2020) . The encephalopathy is most likely a consequence of systemic factors, such as cytokine sickness, hypoxia and metabolic dysfunction due to peripheral organ failure, while the strokes seem to be related more to hypercoagulability and endothelial injury than to SARS-CoV-2 vasculitis affecting brain vessels. In some cases, the possibility of a SARS-CoV-2 encephalitis could not be ruled out based on the potential for the virus to infect neurons (Song et al., 2020) , but definitive clinical and pathological evidence of neurotropism is lacking.
cord-334123-wb45ww7f	1989	A third and earlier study proposed that an RNA pseudoknot is recognized by a DNA binding protein that autogenously regulates translation of its mRNA (McPheeters et al., 1988) . The tRNA-like structures at the 3'' ends of plant viral RNAs provide one example where the pseudoknot format may be necessary to form a substrate that is specifically recognized by an enzyme. Previous structural mapping experiments by Draper and co-workers suggested a model for the 5'' region of the mRNA which constitutes the S4 binding site; it envisions a hairpin helix and loop that encompasses nucleotides 19 to 72. The second study provides evidence that pseudoknot formation in a viral mRNA is required for frameshift suppression of a termination codon that, in turn, allows a fusion protein to be synthesized from two overlapping reading frames. This element encodes a stem-loop structure that starts six nucleotides downstream from the proposed site of frameshifting, near the end of the first reading frame.
cord-336696-c3rbmysh	2020	
cord-339093-mwxkvwaz	2020	It potently neutralized mouse adapted SARS-CoV-2 in wild type mice at a dose as low as 2 mg/kg and exhibited high prophylactic and therapeutic efficacy in a hamster model of SARS-CoV-2 infection, possibly enhanced by its relatively small size. To identify potent neutralizing V H s against SARS-CoV-2, we panned our large (10 11 clones) and diverse phage-displayed human V H antibody library against recombinant RBD. One of those V H s, ab8, in an Fc (human IgG1, crystallizable fragment) fusion format, showed potent neutralization activity and specificity against SARS-CoV-2 both in vitro and in two animal models. They also suggest that the double mutations Q498T/P499Y on RBD did not influence V H -Fc ab8 binding and contribute to the validation of the mouse adapted SARS-CoV-2 model for evaluation of neutralizing antibody efficacy. In conclusion, we identified a fully human antibody V H domain that shows strong competition with ACE2 for binding to RBD and potent neutralization of SARS-CoV-2 in vitro and in two animal models.
cord-342189-ya05m58o	2020	Here, we comprehensively define the interactions between each SARS-CoV-2 protein and human RNAs. We show that 10 viral proteins form highly specific interactions with mRNAs or ncRNAs, including those involved in progressive steps of host cell protein production. We show J o u r n a l P r e -p r o o f 5 that NSP16 binds to the mRNA recognition domains of the U1 and U2 RNA components of the spliceosome and acts to suppress global mRNA splicing in SARS-CoV-2-infected human cells. We identified several pathogenic functions of SARS-CoV-2 in human cells -including global inhibition of host mRNA splicing, protein translation, and membrane protein trafficking -and described the molecular mechanisms by which the virus acts to disrupt these essential cell processes.
cord-345103-b2wkm03g	2020	
cord-350855-gofzhff7	2020	High-sensitivity RNA in situ mapping revealed the highest ACE2 expression in the nose with decreasing expression throughout the lower respiratory tract, paralleled by a striking gradient of SARS-CoV-2 infection in proximal (high) vs distal (low) pulmonary epithelial cultures. COVID-19 autopsied lung studies identified focal disease and, congruent with culture data, SARS-CoV-2-infected ciliated and type 2 pneumocyte cells in airway and alveolar regions, respectively. We measured the relative infectivity of the SARS-CoV-2 GFP virus in primary 283 cells based on the average peak titers and observed that infectivity exhibited the same 284 pattern as the ACE2 expression levels from the upper to lower respiratory tract ( Figure 285 6Bi-6Biv). Gene 1230 expression and in situ protein profiling of candidate SARS-CoV-2 receptors in human 1231 airway epithelial cells and lung tissue