Cell 184, 11711187 e1120 (2021). Escape from neutralizing antibodies by SARS-CoV-2 spike protein variants. Rachel Sealfon, a research scientist at the Flatiron Institute Center for Computational Biology, is also an author of the paper. Scores represent the binding constant (log10 KD) relative to the wild-type reference amino acid. Other examples of mutations that impact the epitopeparatope interface indirectly include mutations in the signal peptide region and at cysteine residues 15 and 136, which form a disulfide bond that staples the NTD amino terminus against the galectin-like -sandwich30. Science 369, 650 (2020). 35, 13481354 (2018). Hundreds packed Killian and Hockfield courts to enjoy student performances, amusement park rides, and food ahead of Inauguration Day. Arguably the first variant of interest defined by the presence of several spike mutations, and referred to as B.1.1.298 (cluster 5), was detected in Denmark spreading among farmed mink and a small number of people20. https://www.preprints.org/manuscript/202101.0132/v1 (2021). 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. N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2. Cherian, S. et al. Over time, the cumulative effects of these mutations may be enough to change how the virus behaves. A novel SARS-CoV-2 variant of concern, B.1.526, identified in New York. Cell 183, 10241042 e1021 (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. An important part of this process will be the preparation of updated vaccines tailored to emerging antigenic variants that are maximally cross-reactive against all circulating variants. Virus genomic sequences are being generated and shared at an unprecedented rate, with more than one million SARS-CoV-2 sequences available via the Global Initiative on Sharing All Influenza Data (GISAID), permitting near real-time surveillance of the unfolding pandemic2. Biol. Other experiments with pseudotyped viruses showed that the B.1.351 variant was also resistant to the neutralizing activity of some mAbs (12 of 17; 70%)67. Each mutation is classified as having evidence for mutations affecting neutralization by either monoclonal antibodies (mAbs) or antibodies in convalescent plasma39 or vaccinated individuals59, and emerging in selection experiments using mAbs40,47,48 or post-infection serum40,47,48. As mentioned earlier, there is evidence indicating that D614G confers a moderate advantage for infectivity8,9 and increases transmissibility10. 20, 591 (2020). J. is funded by the MRC (MR/R024758/1). N439K is noteworthy as it enhances the binding affinity for the ACE2 receptor and reduces the neutralizing activity of some monoclonal antibodies (mAbs) and polyclonal antibodies present in sera from people who have recovered from infection18. The LJI team found these antibodies can neutralize many SARS-CoV-2 variants by binding to vulnerable sites on the viral structure (gray). While many of its genes were already known at that point, the full complement of protein-coding genes was unresolved. Li, Q. et al. Sci. Alessandro M. Carabelli, Thomas P. Peacock, David L. Robertson, Jessica A. Plante, Yang Liu, Pei-Yong Shi, Sandra Isabel, Luca Graa-Miraglia, Susan M. Poutanen, Steven A. Kemp, Dami A. Collier, Ravindra K. Gupta, Marciela M. DeGrace, Elodie Ghedin, Mehul S. Suthar, Kaiming Tao, Philip L. Tzou, Robert W. Shafer, Kizzmekia S. Corbett, Darin K. Edwards, Barney S. Graham, Nature Reviews Microbiology Non-synonymous nucleotide substitutions in protein-coding sequence result in a change in amino acid (referred to as a substitution or replacement), whereas synonymous nucleotide substitutions do not change the amino acid. Similarly, neutralizing activity of sera elicited by the inactivated vaccine Covaxin (Bharat Biotech) against B.1.1.7 viruses was largely preserved87. Garcia-Beltran, W. F. et al. Circulating SARS-CoV-2 spike N439K variants maintain fitness while evading antibody-mediated immunity. Correspondence to Cell https://doi.org/10.1016/j.cell.2021.02.042 (2021). The P.1 lineage has also been associated with a reinfection case in Manaus, Brazil27, indicating it is contributing to antigenic circumvention of what might have been an otherwise effective immune response. 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? 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. Scientists can track mutations as they are passed down through a lineage, a branch of the coronavirus family tree. wrote the article. Resurgence of Omicron BA.2 in SARS-CoV-2 infection-naive Hong Kong 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. The substitutions, insertions or deletions of one or more nucleotides in the virus RNA genome. Prospective mapping of viral mutations that escape antibodies used to treat COVID-19. Preprint at bioRxiv https://doi.org/10.1101/2021.01.25.427948 (2021). ECDC. J. E484 has been identified as an immunodominant spike protein residue, with various substitutions, including E484K, facilitating escape from several mAbs40,47,48 as well as antibodies in convalescent plasma39,40,41,48. Fonager J. et al. The impact of mutations in SARS-CoV-2 spike on viral infectivity and antigenicity. To assess the impact of spike mutations and their immunological role in the global SARS-CoV-2 population, we combined structural analyses with the observed frequency of mutations in circulating variants (Fig. Nat. 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 . Natl Acad. A lineage is a genetically closely related group of virus variants derived from a common ancestor. Emergence of multiple SARS-CoV-2 mutations in an immunocompromised host. 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. Relatively little is known of antigenicity in the S2 subunit, with immunogenicity thought to be impeded by extensive glycan shielding36, and although both linear and cross-reactive conformational S2 epitopes have been described37,38, the biological significance of these is not yet known. 1a,b). By contrast, when tested with convalescent serum, neutralization of the S477N mutant was similar to that of the wild type48. The role of mutation in nucleoproteins of SARS-CoV-2 Temporal signal and the phylodynamic threshold of SARS-CoV-2. However, many sites in the viral genome are under strong functional selection, and so the mutational patterns at those sites will represent the combined action of mutation and selection. SARS-CoV-2 variants, spike mutations and immune escape https://doi.org/10.1093/ve/veaa034 (2020). a: Monitoring an umbrella of SARS-CoV-2 lineages that have similar Spike protein profiles and characterised by a specific set of mutations ( S:Q183E, S:F486P and S:F490S ). Use the Previous and Next buttons to navigate the slides or the slide controller buttons at the end to navigate through each slide. Rev. You may not alter the images provided, other than to crop them to size. https://cov-lineages.org/global_report.html. Scientists from The Federal Research Centre "Fundamentals of Biotechnology" of the Russian Academy of Sciences together with foreign colleagues demonstrated that human 14-3-3 proteins, that are known for their role in replication of many viruses, bind differentially with more often mutating regulatory part of nucleoprotein (N protein) of coronavirus SARS-CoV-2. Recurrent emergence and transmission of a SARS-CoV-2 spike deletion H69/V70. Viruses generally acquire mutations over time, giving rise to new variants. PubMed Science 326, 734736 (2009). Preprint at bioRxiv https://doi.org/10.1101/2021.02.01.429069 (2021). Residue 769 is positioned in a surface-exposed S2 loop, and D769H was found to arise, in linkage with 6970, in an immunocompromised individual treated with convalescent plasma24. 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. Structure-based antibody access scores for the spike protein in the closed and open conformations are shown. https://files.ssi.dk/Mink-cluster-5-short-report_AFO2 (2020). SARS-CoV-2 evolution during treatment of chronic infection. One study reported structural, biophysical and bioinformatics analyses of 15 SARS-CoV-2 RBD-binding neutralizing antibodies31. Preprint at bioRxiv https://doi.org/10.1101/2021.01.26.426986 (2021). Avanzato, V. A. et al. The mRNA technology is very flexible and can accommodate new mutations, says Iwasaki. A group of coronaviruses that share the same inherited set of distinctive.