Volz E, Hill V, McCrone J, et al. SARS-CoV-2 has been acquiring minor random mutations ever since it jumped from animals to humans. Amino acid position 157 has been identified as an epitope residue, with F157A reducing neutralization by the mAb 2489 (ref.34). Cell 183, 10241042 e1021 (2020). 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). 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. What is the Omicron variant? SARS-CoV-2 and Immunosuppression In this article, . Cell 183, 739751.e738 (2020). Bugembe, D. L. et al. http://cov-glue.cvr.gla.ac.uk/#/home (2020). To assess the impacts of mutations on vaccine efficacy, authentic viruses and pseudoviruses possessing particular spike mutations (either individually or in combination) and larger sets of mutations representing variants of concern and other circulating spike mutations have been assessed by neutralization assays with postvaccination sera (Supplementary Table 1). 2a, peaks with consecutive residues with scores greater than 0.8) are centred at residues 444447 and residues 498500. When an observation includes a deletion, this is indicated by a red cross. DMS data on ACE2-binding affinity19 are shown in shades of red or blue representing higher or lower ACE2 affinity, respectively. Investigations with pseudoviruses possessing RBD mutations carried by variants of concern demonstrated that the neutralizing activity of plasma from vaccinated individuals showed a small but significant decreases of onefold to threefold against E484K, N501Y or the K417N+E484K+N501Y triple mutant59. In a live-virus neutralization assay, neutralizing titres of ChAdOx1 nCoV-19 (OxfordAstraZeneca) postvaccination sera were nine times lower than titres against the B.1.1.7 lineage relative to a canonical non-B.1.1.7 lineage (Wuhan-Hu-1 with the S247R spike mutation)86. Collier, D. A. et al. As new variants with unforeseen combinations of mutations continue to emerge, such insights will allow predictions of virus phenotype. Genome sequencing and analysis of an emergent SARS-CoV-2 variant characterized by multiple spike protein mutations detected from the Central Visayas Region of the Philippines. Starr, T. N. et al. Tracking changes in SARS-CoV-2 spike: evidence that D614G increases infectivity of the COVID-19 virus. PubMed The SARS-CoV-2 genome consists of nearly 30,000 RNA bases. Efficacy of the ChAdOx1 nCoV-19 Covid-19 Vaccine against the B.1.351 Variant. Martin, D. P. et al. 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. 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). Analyses integrating genomic and mortality data estimate that P.1 may be 1.7 to 2.4-fold more transmissible and that previous infection by non-P.1 SARS-CoV-2 provides 5479% of the protection against P.1 infection compared with non-P.1 lineages71. Cross-reactive immunity between circulating lineages can be assessed by measuring the ability of sera to neutralize panels of circulating viruses. Spike E484K Mutation in the First SARS-CoV-2 Reinfection Case Confirmed in Brazil, 2020. https://virological.org/t/spike-e484k-mutation-in-the-first-sars-cov-2-reinfection-case-confirmed-in-brazil-2020/584 (2021). https://doi.org/10.1038/s41591-021-01270-4 (2021). How do variants of SARS-CoV-2, the virus that causes COVID-19, get their names? SARS-CoV-2 spreads primarily through human-to-human transmission, but there is evidence of transmission between humans and animals. Whereas K417 is described in the epitopes of RBD class 1 and class 2 antibodies31, alterations to K417 tend to affect class 1 antibody binding and are therefore somewhat less important for the polyclonal antibody response to the RBD, which is dominated by class 2 antibody responses, which are more susceptible to substitutions such as E484K44,58,59. Across the spike protein, some mutations that confer escape to neutralizing mAbs have little impact on serum antibody binding39,40,44, possibly because those mAbs are rare in polyclonal sera, targeting subdominant epitopes12,39,44. 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. While the idea of "viral mutation" may sound concerning, it's important to understand that many of these mutations are minor, and don't have an overall impact on how fast a virus spreads or potentially how severe a viral infection might be. Another variant within the A lineage, the prevalence of which is rising in Uganda (A.23.1), shares with the B.1.1.7 lineage a substitution at position 681 within the furin cleavage site (P681R has been found in the A lineage, whereas P681H has been found in the B.1.1.7 lineage), and additionally has the amino acid substitutions R102I, F157L, V367F and Q613H. 5b. Faria, N. R. et al. The N-terminal domain of spike glycoprotein mediates SARS-CoV-2 infection by associating with L-SIGN and DC-SIGN. However, a DMS study39 did not find that the mutation N439K significantly alters neutralization by polyclonal antibodies in plasma, in contrast to previous studies that found that N439K reduced neutralization by mAbs and convalescent plasma18. In addition to N3, high-scoring residues (greater than 0.7) are found at positions 2226 (N1), 70 (N2), 173187 (N4), 207213 (Fig. The six strains of SARS-CoV-2 -- ScienceDaily Information on how spike mutations affect antigenic profiles can be derived from structural studies, mutations identified in viruses exposed to mAbs or plasma containing polyclonal antibodies, targeted investigations of variants using site-directed mutagenesis and deep mutational scanning (DMS) experiments that systematically investigate the possibility of mutations arising. A protein with oligosaccharide chains (glycans) covalently attached to amino acid side chains. To nail down which parts of the SARS-CoV-2 genome actually contain genes, the researchers performed a type of study known as comparative genomics, in which they compare the genomes of similar viruses. 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. 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. A list of members and their affiliations appears in Supplementary information. Recent studies have shown the potential selective pressure exerted by convalescent plasma and mAb treatments on SARS-CoV-2 evolution in immunocompromised individuals24,25,26. Scores rescaled between 0 and 1 are plotted for the closed conformation in Fig. 2c, yellow). Nonaka, C. K. V. et al. The name of the mutation, del 69-70, or 69-70 del, or other similar notations, refers to the . SARS-CoV-2 variants, spike mutations and immune escape SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma. The substitutions T20N and P26S also occur in or near the NTD supersite30 at residues with high antibody accessibility scores (Fig. Silver, Z. Image from the Saphire Lab, La Jolla Institute for Immunology. 3. 5b), and T20N introduces a potential glycosylation site that could result in glycan shielding (Box2) of part of the supersite. Science https://doi.org/10.1126/science.abd0831 (2020). Tracking SARS-CoV-2 variants - WHO For example, viruses of lineage B.1.525, which has been observed in several countries, albeit at low frequency to date, have NTD deletions H69V70 and Y144 in common with viruses of the B.1.1.7 lineage; E484K in common with the B.1.351 and P.1 lineages; and spike amino acid substitutions Q52R, Q677H and F888L73. A lineage is a genetically closely related group of virus variants derived from a common ancestor. In the open form, residues close to the ACE2-binding site (405, 415, 416, 417 and 468) become much more exposed on both the upright RBD and the clockwise adjacent closed RBD (Fig. The first strain of SARS-CoV-2, the virus that causes COVID-19, was detected in Wuhan, China in December 2019. Of these, the Y453F substitution occurs at a residue within the ACE2 footprint and has been shown by DMS to increase ACE2 affinity19. The Coronavirus Is Mutating. What Does That Mean for a Vaccine? Med. Identification of SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization. COG-UK Mutation Explorer: D614G refers to an amino acid mutation in this protein that has become increasingly common in SARS-CoV-2 viruses from around the world. 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. D614G spike mutation increases SARS CoV-2 susceptibility to neutralization. Tchesnokova, V. et al. Zheng, Z. et al. This indicates that, generally, the amino acid positions at which antibody escape mutations have been detected in vitro tolerate mutations at least to some degree in vivo. 1. c | A close-up view of the receptor-binding domain (RBD) bound to ACE2 (RCSB Protein Data Bank ID 6M0J95), with RBD residues shown as spheres coloured by amino acid variant frequency and ACE2 shown in gold. To monitor vaccine efficacy and to better understand the implications of antigenic variation for vaccine effectiveness, it will be important to collect information on vaccine status and viral genome sequence data from individuals infected with SARS-CoV-2. Experimental studies are needed to figure out the functions of the uncharacterized genes, and by determining which ones are real, we allow other researchers to focus their attention on those genes rather than spend their time on something that doesnt even get translated into protein.. Here's how scientists are tracking the genetic evolution of A few other regions were suspected to encode proteins, but they had not been definitively classified as protein-coding genes. also acknowledges support of the Wellcome Trust (220977/Z/20/Z). You are using a browser version with limited support for CSS. Science 371, 11391142 (2021). In this video, Iwasaki and Grubaugh discuss the science behind the SARS-CoV-2 mutations and explain why its important to continue wearing masks, avoiding crowds, and washing your hands. Cell 182, 12951310.e1220 (2020). The phenomenon by which the host immune response against a viral particle is mostly focused on a few antigens and mediated by potently neutralizing antibodies. Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Chi, X. et al. The role of mutation in nucleoproteins of SARS-CoV-2 The emergence of SARS-CoV-2 in Europe and North America. Acquisition of the L452R mutation in the ACE2-binding interface of spike protein triggers recent massive expansion of SARS-Cov-2 variants. and D.L.R. Greaney, A. J. et al. Mobilisation and analyses of publicly available SARS-CoV-2 data for The substitutions, insertions or deletions of one or more nucleotides in the virus RNA genome. Structural and functional analysis of the D614G SARS-CoV-2 spike protein variant. Greaney, A. J. 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. Experimental data on the emergence of mutations under selective pressure from polyclonal antibodies are relatively rare, although these trends for higher scores associated with such mutations indicate that information from structural analysis approaches of this kind can contribute to the ranking of residues at which substitutions are likely to impact the polyclonal antibody response. Baum, A. et al. A cocktail of antibodies for COVID-19 therapy. J. Virol. Nature 581, 215220 (2020). Therefore, sequencing of viruses associated with prolonged infections will provide useful information on mutations that could contribute to increased transmissibility or escape from vaccine-mediated immunity. These data indicate that NVX-CoV2373 and JNJ-78436735 are clinically efficacious against the B.1.1.7 variant and variants circulating in the USA, and are consistent in that the B.1.351 variant is associated with a larger reduction in vaccine efficacy. 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. 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. 2c, green). Glycans are bulky sugar molecules that may shield epitopes from antibody binding. Get the most important science stories of the day, free in your inbox. Cell 183, 19011912 e1909 (2020). 1 ). Nat. Cell 182, 812827 e819 (2020). 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. This is because although high-effect mutations that contribute to virus adaption and fitness do occur, they tend to be in the minority compared with tolerated low-effect or no-effect neutral amino acid changes4. Now, after performing an extensive comparative genomics study, MIT researchers have generated what they describe as the most accurate and complete gene annotation of the SARS-CoV-2 genome. The most frequently detected NTD deletion is the two-residue deletion at positions 69 and 70 (6970), present in 45,898 sequences. A new variant carrying E484K currently designated A.VOI.V2 was recently identified in Angola from cases involving travel from Tanzania79. and D.L.R. Cell 78, 779784 e775 (2020). Fonager J. et al. This approach calculates a structure-based epitope score, which approximates antibody accessibility for each amino acid position. reviewed and/or edited the manuscript before submission. https://virological.org/t/sars-cov-2-reinfection-by-the-new-variant-of-concern-voc-p-1-in-amazonas-brazil/596 (2021). 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. Kemp, S. A. et al. 5, 562569 (2020). Comparative genomics and D.L.R. As of April 2021, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), the causative agent of COVID-19, accounted for more than 143 million infections and more than three million deaths worldwide1. CAS 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. Nature https://doi.org/10.1038/s41586-021-03471-w (2021). Massachusetts Institute of Technology77 Massachusetts Avenue, Cambridge, MA, USA. Substitutions at amino acid positions 417 and 453 are described in the next section in the context of variants of concern. Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape. Anyone you share the following link with will be able to read this content: Sorry, a shareable link is not currently available for this article. The authors thank all of the researchers who have shared genome data openly via the Global Initiative on Sharing All Influenza Data (GISAID). The researchers also analyzed mutations that have arisen in variants of concern, such as the B.1.1.7 strain from England, the P.1 strain from Brazil, and the B.1.351 strain from South Africa. . SARS-CoV-2 variants of concern as of 20 April 2023 Preprint at bioRxiv https://doi.org/10.1101/2021.01.15.426849 (2021). CD, connecting domain; CT cytoplasmic tail; FP, fusion peptide; RBM, receptor-binding motif; TM, transmembrane domain. There have been a number of missense mutations observed of SARS-CoV-2. Sapkal, G. N. et al. Virusdisease 31, 1321 (2020).