27, 622625 (2021). But, says Akiko Iwasaki, PhD, a Yale immunobiologist and leading COVID-19 researcher, When viruses enter the host cells and replicate and make copies of their genomes, they inevitably introduce some errors into the code. Iwasaki, who studies the mechanisms of immune defense against viruses, compares the changes introduced by these errors to a faulty spell-checker. The research center will support two nonprofits and four government agencies in designing randomized evaluations on housing stability, procedural justice, transportation, income assistance, and more. L452R independently appeared in several other lineages around the globe between December 2020 and February 2021, indicating that this amino acid substitution is probably the result of viral adaptation due to increasing immunity in the population75. Similarly, the single-dose vaccine JNJ-78436735 (Johnson & Johnson/Janssen) has been shown to provide 72% protection against moderate to severe SARS-CoV-2 infections in the USA, but the proportion significantly decreased to 57% in South Africa (at a time when the B.1.351 variant was widespread)92. Globally, the highest number of amino acid variants, mapped against the Wuhan-Hu-1 reference sequence (MN908947), are recorded at amino acid positions 614, 222 and 18 (Fig. In late 2020 and early 2021, the emergence and sustained transmission of lineages with mutations that affect the characteristics of the virus received much attention, most notably lineages B.1.1.7, B.1.351 and P.1 (also known as 501Y.V1, 501Y.V2 and 501Y.V3, respectively). And, we know all too well that SARS-CoV-2 has spread quickly throughout the world. Correspondence to In one example, the researchers identified a region of the nucleocapsid protein, which surrounds the viral genetic material, that had many more mutations than expected from its historical evolution patterns. Repeated amino acid substitutions at position 677 and the independent emergence of Q677H in several lineages in the USA provides strong evidence of adaptation, potentially through an effect of this mutation on the proximal polybasic furin cleavage site, although further experiments are required to determine its impact74. https://cov-lineages.org/global_report.html. Of the four RDRs, RDR1, RDR2 and RDR4 correspond to NTD loops N2, N3 and N5, whereas RDR3 falls between N4 and N5 in another accessible loop (Fig. 4a) (among 426,623 high-quality sequences retrieved from the GISAID database on 3 February 2021 and processed using CoV-GLUE). Annavajhala, M. K. et al. Postvaccination sera from individuals who received two doses of mRNA-1273 (28 days apart) showed reduced neutralization of the B.1.351 variant (6.4-fold reduction)88. They have made the annotated gene set and their mutation classifications available in the University of California at Santa Cruz Genome Browser for other researchers who wish to use it. For B.1.1.7, scissors mark the approximate position of substitution P681H within the furin cleavage site, which is absent from the structural model. This insertion, which also introduced a new glycosylation motif in the vicinity of RDR4, is predicted to alter the structure of the antigenic N3 and N5 NTD loops41. The emergence of SARS-CoV-2 in late 2019 was followed by a period of relative evolutionary stasis lasting about 11 months. The scissors represent the S1S2 boundary at amino acid position 685. To complement the experimental data provided by neutralization assays, there is emerging evidence from clinical trials on the impact of variants on vaccine efficacy. Zahradnk, J. et al. . In early 2020, a few months after the Covid-19 pandemic began, scientists were able to sequence the full genome of SARS-CoV-2, the virus that causes the Covid-19 infection. Soh, W. T. et al. In their study, which appears today in Nature Communications, they confirmed several protein-coding genes and found that a few others that had been suggested as genes do not code for any proteins. Comparisons with reporting of antibody footprints and the impact of mutations on antigenicity indicate that residues with mutations described as affecting recognition by mAbs or antibodies in convalescent plasma (Fig. Hensley, S. E. et al. The researchers performed their analysis on SARS-CoV-2, SARS-CoV (which caused the 2003 SARS outbreak), and 42 strains of bat sarbecoviruses. 1b). The B.1.427 and B.1.429 variants carry an antigenically noteworthy substitution, L452R75, which has been shown to reduce neutralization by several mAbs43,45,48,59 and convalescent plasma43. By convention, an amino acid substitution is written in the form N501Y to denote the wild-type amino acid (N (asparagine)) and the substituted amino acid (Y (tyrosine)) at site 501 in the amino acid sequence. a | Structure-based antibody accessibility scores for each spike protein ectodomain residue in the closed form were calculated with BEpro49. And even if the effectiveness of vaccines dropped to, say, 75 or 85%, that would still provide important protection and prevent severe cases of the COVID-19 from occurring. To evaluate potential antigenicity across the spike protein, we analysed the protein using BEpro, a program for the prediction of conformational epitopes based on tertiary structure49. When residues belong to epitopes of multiple classes, priority colouring is given to antibodies that block ACE2 and bind the closed spike protein. Choi, B. et al. SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo. is funded by the UK Biotechnology and Biological Sciences Research Council (BB/R012679/1). The COVID-19 Genomics UK (COG-UK) Consortium is supported by funding from the UK Medical Research Council (MRC), part of UK Research and Innovation, the UK National Institute of Health Research and Genome Research Limited, operating as the Wellcome Sanger Institute. This variant carries several amino acid substitutions in the spike protein and three deletions in the NTD, some of which are within the antigenic supersite79. PubMed Central As new variants with unforeseen combinations of mutations continue to emerge, such insights will allow predictions of virus phenotype. 2b. Taken together, these data indicate that E484K is the primary determinant of the decreases in neutralization titres, which distinguish P.1, P.2 and the three B.1.351 variants from the other pseudoviruses tested. McCarthy, K. R. et al. Monophyletic clusters of viruses assigned on the basis of the severe acute reparatory syndrome coronavirus 2 (SARS-CoV-2) global phylogenetic tree. Development of vaccines against SARS-CoV-2 has been rapid, but the rise of variants forces scientists to frequently modify treatments. The S1S2 boundary is at amino acid position 685. b | Spike protein monomer displaying an upright receptor-binding domain (RBD). The rate of evolution of SARS-CoV-2 from December 2019 to October 2020 was consistent with the virus acquiring approximately two mutations per month in the global population15,16. We have all the tools needed to stop the spread of these new variants, Grubaugh emphasized. What is the difference between a variant of interest and a variant of concern? 1a), and high levels of amino acid substitutions are observed at some amino acid positions where mutations are described as affecting recognition by antibodies in convalescent plasma, including positions 439 and 484. April 24, 2023. Pseudovirus and live-virus neutralization assays showed that the neutralizing activity of sera from individuals after the two doses of the ChaAdOx1 vaccine against the B.1.351 variant was reduced or abrogated86. Sars-Cov-2, the official name of the virus that causes the disease Covid-19, and continues to blaze a path of destruction across the globe, is mutating. A group of coronaviruses that share the same inherited set of distinctive. There is also evidence that this lineage may be associated with a higher viral load62. This lineage has spread widely in Europe and is reported to have originated in Spain52. The virus causing the COVID-19 pandemic, SARS-CoV-2, presents at least six strains. 5, 14031407 (2020). https://cov-lineages.org/global_report.html (2020). You are using a browser version with limited support for CSS. http://cov-glue.cvr.gla.ac.uk/#/home (2020). Watanabe, Y., Allen, J. D., Wrapp, D., McLellan, J. S. & Crispin, M. Site-specific glycan analysis of the SARS-CoV-2 spike. 1b). 2a, asterisk). This finding further demonstrates the structural plasticity of the NTD and indicates that insertions and the acquisition of additional glycosylation motifs in the NTD are further mechanisms in addition to deletion that lead to immune evasion. Nature 581, 215220 (2020). Here's what scientists are watching for: Like all viruses, SARS-CoV-2 is mutating as it passes from person to person. SARS-CoV-2 variants of concern tend to emerge mutations in the S1 unit of the spike protein, which includes the RBDs and is responsible for binding to the ACE2 receptor. Med. The H69V70 deletion has been identified in variants associated with immune escape in immunocompromised individuals treated with convalescent plasma24. Nature https://doi.org/10.1038/s41586-021-03471-w (2021). Science https://doi.org/10.1126/science.abd0831 (2020). & McCauley, J. GISAID: Global initiative on sharing all influenza datafrom vision to reality. For each residue, the calculated score accounts for the local protein structure: half-sphere exposure measures and propensity scores each depend on all atoms within 816 of the target residue, with weighting towards closer atoms. Spike amino acid residues are coloured according to the frequency of amino acid substitutions or deletions. J. 2c, green). Madhi, S. A. et al. W.T.H. Nature 584, 450456 (2020). Cell 78, 779784 e775 (2020). Should You Get an Additional COVID-19 Bivalent Booster. Tracking changes in SARS-CoV-2 spike: evidence that D614G increases infectivity of the COVID-19 virus. Zhan, X.-Y. The co-occurrence of K417N, E484K and these NTD substitutions suggests that lineage B.1.351 may overcome the polyclonal antibody response by reducing neutralization by class 1 and class 2 RBD-specific antibodies and NTD-specific antibodies (Fig. Accessible amino-terminal domain (NTD) loops N1N5 are labelled, and a loop falling between these is indicated with an asterisk. As mentioned earlier, there is evidence indicating that D614G confers a moderate advantage for infectivity8,9 and increases transmissibility10. https://virological.org/t/preliminary-genomic-characterisation-of-an-emergent-sars-cov-2-lineage-in-the-uk-defined-by-a-novel-set-of-spike-mutations/563 (2020). 3). mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants. As highly deleterious mutations are rapidly purged, most mutations observed in genomes sampled from circulating SARS-CoV-2 virions are expected to be either neutral or mildly deleterious. Tablizo, F. A. et al. The LJI team found these antibodies can neutralize many SARS-CoV-2 variants by binding to vulnerable sites on the viral structure (gray). What are variants of SARS-COV-2, the virus that causes COVID-19? The six strains of SARS-CoV-2 -- ScienceDaily A new variant carrying E484K currently designated A.VOI.V2 was recently identified in Angola from cases involving travel from Tanzania79. Viral epitope profiling of COVID-19 patients reveals cross-reactivity and correlates of severity. For example, the spike protein amino acid change D614G was noted to be increasing in frequency in April 2020 and to have emerged several times in the global SARS-CoV-2 population, and the coding sequence exhibits a high dN/dS ratio, suggesting positive selection at the codon position 614 (refs6,7). ECDC. COG-UK Mutation Explorer: The magenta spheres represent glycans, and the magenta triangles represent potantial N-linked glycosylation sites. The substitution L18F has occurred ~21 times in the global population53 and is associated with escape from multiple NTD-binding mAbs30. Mobilisation and analyses of publicly available SARS-CoV-2 data for SARS-CoV-2 variants, spike mutations and immune escape One study identified four recurrently deleted regions (RDRs) within the NTD and tested five frequently observed deletions within these: 6970 (RDR1), 141144 and 146 (RDR2), 210 (RDR3) and 243244 (RDR4)42. Preprint at medRxiv https://doi.org/10.1101/2021.02.08.21251393 (2021). In addition to their antigenic effect, both K417N and K417T are expected to moderately decrease ACE2-binding affinity19 (Fig. The spike protein mediates attachment of the virus to host cell-surface receptors and fusion between virus and cell membranes11 (Box1). Volz E, Hill V, McCrone J, et al. The escape fraction (that is, a quantitative measure of the extent to which a mutation reduced polyclonal antibody binding) averaged across all amino acid substitutions at a residue (plasma average) and the maximally resistant substitution (plasma max) are indicated. Comparison of the differing extents to which variants affect neutralization by postvaccination serum is complicated by the different methods used in various studies. Nat. SARS-CoV-2 Mutations Explained - Discovery's Edge But luckily with vaccines, you dont just create one antibodyor two or threeyou create many different antibodies that recognize different parts of the virus.. Sign up for the Nature Briefing newsletter what matters in science, free to your inbox daily. Nature https://doi.org/10.1038/s41586-021-03412-7 (2021). Tracking SARS-CoV-2 Spike mutations - Los Alamos National Laboratory Emergence and rapid spread of a new severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2) lineage with multiple spike mutations in South Africa. A new method could provide detailed information about internal structures, voids, and cracks, based solely on data about exterior conditions. In addition to understanding the transmissibility and pathogenicity of these emerging variants, it is crucially important to characterize their antigenicity and the level of cross-protection provided by infection by earlier viruses that are genetically and antigenically similar to the virus that first emerged in December 2019 and which is used in all of the current vaccine preparations. Bioinformatics 24, 14591460 (2008). ACS Cent. Furthermore, epitope mapping of mAbs isolated from postvaccination sera showed they targeted a range of RBD epitopes similar to those isolated from naturally infected individuals59. Multiple SARS-CoV-2 variants escape neutralization by vaccine-induced humoral immunity. Wrobel, A. G. et al. http://sars2.cvr.gla.ac.uk/cog-uk/, COVID-19 Genomics UK (COG-UK) Consortium: How do variants of SARS-CoV-2, the virus that causes COVID-19, get their names? More details of the frequency and geographic distribution of the P1 lineage can be found at the Pango lineages website72. One study described the structure of five previously unmodelled, protruding NTD loops, denoting them N1N5. Singer, J., Gifford, R., Cotten, M. & Robertson, D. L. CoV-GLUE: A Web Application for Tracking SARS-CoV-2 Genomic Variation. Coronavirus disease (COVID-19): Variants of SARS-COV-2 Although significant interperson and intraperson heterogeneity in the impact of mutations on neutralization by polyclonal serum has been described, the mutations that reduce antibody binding the most occur at a relatively small number of RBD residues, indicating substantial immunodominance within the RBD39. Within the RBD, the two areas with high structure-based antibody accessibility scores for the closed spike structure (Fig. The residues comprising the receptor-binding motif are revealed on the upright RBD, enabling binding to ACE2, which induces a progressively more open structure until a fully open, three-ACE2-bound structure is formed, initiating S2 unsheathing and membrane fusion101. Sweredoski, M. J. Scores rescaled between 0 and 1 are plotted for the closed conformation in Fig. Viruses naturally change over time through the process of mutation. In addition to E484K, further mutations that are shared by each of the three B.1.351 variants, but are not possessed by the P.1. Modelling approaches to predict the evolutionary trajectories of emerging variants based on an understanding of the phenotypic effects of mutations will assist this process, as is the case for influenza virus94. Shrock, E. et al. PubMedGoogle Scholar. Cell Host Microbe 29, 4457 e49 (2021). A mutation (also referred to as viral mutation or genetic mutation) of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus is a change in the genetic sequence of. Many seniors now eligible to get another COVID booster, CDC says Residues with at least 100 sequences possessing a substitution or deletion are coloured according to the frequency scale shown, with the remainder shaded grey. 2c, yellow). Consequently, mutations that affect the antigenicity of the spike protein are of particular importance. Garcia-Beltran, W. F. et al. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. The gene has RNA bases that overlap with ORF3a but occur in a different reading frame. Several animals like mink, dogs, domestic cats, lions, tigers and raccoon dogs have tested positive for SARS-CoV-2 after contact with infected humans. Convergent evolution of SARS-CoV-2 spike mutations, L452R, E484Q and P681R, in the second wave of COVID-19 in Maharashtra, India. Virus Evol. The presence of a polybasic furin cleavage site at the S1S2 boundary, which is unique within the subgenus Sarbecovirus, is important for infectivity and virulence100, with furin cleavage facilitating the conformational change required for receptor binding50. One study described the emergence of escape mutations in viruses exposed to convalescent plasma from two individuals, one of which selected for NTD mutations only (N148S, K150R, K150E, K150T, K150Q and S151P)40. 4a).The SARS-CoV-2 spike protein is post-translationally cleaved by mammalian furin into two subunits: S1 and S2 (Fig. Currently, scientists are optimistic that the two mRNA vaccines available in the U.S.Pfizer-BioNTech and Modernawill continue to provide protection. They also determined that the region that encodes a gene called ORF3a also encodes an additional gene, which they name ORF3c. ISSN 1740-1534 (online) 2a, peaks with consecutive residues with scores greater than 0.8) are centred at residues 444447 and residues 498500. The lineage has been associated with a rapidly increasing proportion of reported SARS-CoV-2 cases, and phylogenetic analyses indicate that this lineage was associated with a growth rate estimated to be 4070% higher than that of other lineages60,61. Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike. Of these positions, 446 occurs in a location in the spike structure that is predicted to be highly antigenic, and substitutions at this site are described as affecting neutralization by both mAbs and antibodies present in polyclonal serum39,43,46,48. W.T.H., A.M.C. 2b). In this video, Iwasaki and Grubaugh discuss the science behind the SARS-CoV-2 mutations and explain why it's important to continue wearing masks, avoiding crowds, and washing your hands. 4a). The B.1.1.298 lineage also has 6970, an amino-terminal domain (NTD) deletion that has emerged several times across the global SARS-CoV-2 population, including in the second N439K lineage, B.1.258. Meredith, L. W. et al. Lancet https://doi.org/10.1016/S0140-6736(21)00628-0 (2021). https://doi.org/10.1038/s41591-021-01270-4 (2021). Cell https://doi.org/10.1016/j.cell.2021.03.028 (2021). Epitope scores are particularly high for residues with mutations described as emerging during exposure to convalescent plasma40,41 (Supplementary Fig. In studies that identified the emergence of antibody escape mutations in virus populations exposed to convalescent plasma, mutations were roughly evenly distributed between the RBD and the NTD (Fig. Previous studies of SARS-CoV-2 variants have also shown that not every variant remains viable for the same duration on shipping materials, suggesting a link between genetic mutations and viral . Cell Host Microbe 29, 2331.E24 (2021). Kemp, S. A. et al. Resende, P. C. et al. Molnupiravir-induced elevated mutation rates have been shown to decrease viral load in animal models. Lineage P.1 is characterized by the presence of several amino acid substitutions in the spike protein: L18F, T20N, P26S, D138Y, R190S, K417T, E484K, N501Y, H655Y and T1027I69. This coincided with the emergence of variants with higher numbers of mutations relative to previous circulating variants. Greater understanding of the correlates of immune protection is required to provide a context for the results of studies reporting changes in neutralization. Acquisition of the L452R mutation in the ACE2-binding interface of spike protein triggers recent massive expansion of SARS-Cov-2 variants. Cross-reactive immunity between circulating lineages can be assessed by measuring the ability of sera to neutralize panels of circulating viruses. A SARS-CoV-2 lineage A variant (A.23.1) with altered spike has emerged and is dominating the current Uganda epidemic. Given that therapeutics (vaccines and antibody-based therapies) target mainly the SARS-CoV-2 spike protein, the selection pressures that favour the emergence of new variants carrying immune escape mutations generated in chronic infections24,25,26 will be similar to those selecting for mutations that allow reinfections within the wider population27,28,29. Blood serum of a previously infected individual that usually contains a mixture of different antibodies referred to as polyclonal antibodies. The substitutions, insertions or deletions of one or more nucleotides in the virus RNA genome. 2022). . Preprint at medRxiv https://doi.org/10.1101/2020.10.25.20219063 (2020). Biol. https://doi.org/10.1056/NEJMoa2102214 (2021). Virus Evol. Amino acid substitutions that alter the epitope. The distance in angstroms to the ACE2-contacting residues that form the receptor-binding site (RBS) is shown in shades of orange; each residue is classified as having evidence for mutations affecting neutralization by either monoclonal antibodies (mAbs)40,43,47,48 or polyclonal antibodies in plasma from previously infected individuals (convalescent)39,40,41,43,48 or vaccinated individuals59 (mAb effect and plasma effect, respectively). The first genomes belonging to the B.1.1.7 lineage were sequenced in the south of England in September 2020. The N-terminal domain of spike glycoprotein mediates SARS-CoV-2 infection by associating with L-SIGN and DC-SIGN. SARS-CoV-2 Reinfection by the New Variant of Concern (VOC) P.1 in Amazonas, Brazil. Prospective mapping of viral mutations that escape antibodies used to treat COVID-19. Nonetheless, there is a rapidly expanding knowledge base regarding the effect of SARS-CoV-2 spike mutations on antigenicity and other aspects of virus biology. ECDC. Global Report Investigating Novel Coronavirus Haplotypes. The half-maximal inhibitory concentration, a quantitative measure that indicates how much of an inhibitory substance (for example, postvaccination serum) is required to inhibit a biological process (for example, virus forming plaques or regions of infected cells in culture) by 50%. 3. A relative lack of glycan shielding may contribute to the immunodominance of the RBD33. Scores represent binding constants (log10 KD) relative to the wild-type reference amino acid. 18, 10611063 (2021). The B.1.1.7 spike mutations have been shown to diminish neutralization of a higher proportion of NTD-specific neutralizing antibodies (9 of 10; 90%) than RBD-specific neutralizing antibodies (5 of 31; 16%)63. 1a,b): ACE2-blocking antibodies that bind the spike protein in the open conformation (class 1); ACE2-blocking antibodies that bind the RBD in both the open conformation and the closed conformation (class 2); antibodies that do not block ACE2 and bind the RBD in both the open conformation and the closed conformation (class 3); and neutralizing antibodies that bind outside the ACE2 site and only in the open conformation (class 4)31. Wagner, C., Hodcroft, E., Bell, S. M., Neher, R. & Bedford, T. Resurgence of SARS-CoV-2 19B Clade Corresponds with Possible Convergent Evolution. eLife https://doi.org/10.7554/eLife.61312 (2020). Hou, Y. J. et al. Google Scholar. A limitation of this approach is that it does not account for glycan shielding of residues and likely overestimates scores at the base of the ectodomain for residues closest to the carboxy terminus. A "mutation" is just a change in a virus's genetic code. A year after the first case of COVID-19 was reported in the U.S., more than 26 million Americans are confirmed to have had this disease, caused by the SARS-CoV-2 virus. Hundreds packed Killian and Hockfield courts to enjoy student performances, amusement park rides, and food ahead of Inauguration Day. While many of its genes were already known at that point, the full complement of protein-coding genes was unresolved. However, there is growing evidence that mutations that change the antigenic phenotype of SARS-CoV-2 are circulating and affect immune recognition to a degree that requires immediate attention. USA 108, E1417 (2011). Baum, A. et al. Evol. The other substitution, S477N, is estimated to have emerged at least seven times in the global SARS-CoV-2 population and has persisted at a frequency of between 4% and 7% of sequences globally since mid-June 2020 (ref.53). Notability criteria. Preprint at medRxiv https://doi.org/10.1101/2021.02.23.21252259 (2021). Pseudoviruses carrying the set of B.1.1.7 spike mutations evaluated with postvaccination serum from individuals who received the BNT162b2 vaccine (two doses)63,78,84 or mRNA-1273 vaccine (two doses)63 exhibited only a modest reduction in neutralization titres (less than threefold). How Do Viruses Mutate and What it Means for a Vaccine? Escape mutations emerging in viruses exposed to convalescent plasma have been identified in both the NTD (F140, N148S, K150R, K150E, K150T, K150Q and S151P) and the RBD (K444R, K444N, K444Q, V445E and E484K)40,41 (Fig. Although our understanding of the functional consequences of spike mutations is rapidly expanding, much of this knowledge involves the reactive investigation of amino acid changes identified as rapidly increasing in frequency or being associated with unusual epidemiological characteristics. A Novel Variant of Interest of SARS-CoV-2 with Multiple Spike Mutations Detected Through Travel Surveillance in Africa. Whereas this first lineage with N439K (designated B.1.141 with the Pango nomenclature system17) quickly became extinct, another lineage that independently acquired N439K (B.1.258) emerged and circulated widely in many European countries18. 5b). N. Engl. In the NTD, most of the evidence for immune evasion focuses on a region centred at a conformational epitope consisting of residues 140156 (N3 loop) and 246260 (N5 loop), which includes the epitope of the antibody 4A832 (Fig. Efficacy of the ChAdOx1 nCoV-19 Covid-19 Vaccine against the B.1.351 Variant. Volz, E. et al. 2c), and residues 978984, which become more accessible on the monomer anticlockwise adjacent to the upright RBD monomer (Fig. https://nextstrain.org/ncov/global?c=gt-S_477&gmax=24271&gmin=22482 (2021). Proc. The specific parts of an antigen recognized by the immune system: antibodies, B cells or T cells. The use of pathogen genomes on this scale to track the spread of the virus internationally, study local outbreaks and inform public health policy signifies a new age in virus genomic investigations3. A comprehensive map of the SARS-CoV-2 genome Preliminary Genomic Characterisation of an Emergent SARS-CoV-2 Lineage in the UK Defined by a Novel set of Spike Mutations. As with other coronaviruses, the entry of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) into host cells is mediated by the transmembrane spike glycoprotein, which forms homotrimers on the surface of the virion. Dis. Cell 182, 12841294.e1289 (2020). Deletions in the NTD have been observed repeatedly in the evolution of SARS-CoV-2 and have been described as changing NTD antigenicity30,41,42. https://virological.org/t/phylogenetic-relationship-of-sars-cov-2-sequences-from-amazonas-with-emerging-brazilian-variants-harboring-mutations-e484k-and-n501y-in-the-spike-protein/585 (2021). Emergence of multiple SARS-CoV-2 mutations in an immunocompromised host. Rees-Spear, C. et al. Rev. Therefore, SARS-CoV-2 has a higher fidelity in its.

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