88
views
0
recommends
+1 Recommend
1 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      SARS-CoV-2 variants, spike mutations and immune escape

      review-article

      Read this article at

      ScienceOpenPublisherPMC
      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Although most mutations in the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome are expected to be either deleterious and swiftly purged or relatively neutral, a small proportion will affect functional properties and may alter infectivity, disease severity or interactions with host immunity. The emergence of SARS-CoV-2 in late 2019 was followed by a period of relative evolutionary stasis lasting about 11 months. Since late 2020, however, SARS-CoV-2 evolution has been characterized by the emergence of sets of mutations, in the context of ‘variants of concern’, that impact virus characteristics, including transmissibility and antigenicity, probably in response to the changing immune profile of the human population. There is emerging evidence of reduced neutralization of some SARS-CoV-2 variants by postvaccination serum; however, a greater understanding of correlates of protection is required to evaluate how this may impact vaccine effectiveness. Nonetheless, manufacturers are preparing platforms for a possible update of vaccine sequences, and it is crucial that surveillance of genetic and antigenic changes in the global virus population is done alongside experiments to elucidate the phenotypic impacts of mutations. In this Review, we summarize the literature on mutations of the SARS-CoV-2 spike protein, the primary antigen, focusing on their impacts on antigenicity and contextualizing them in the protein structure, and discuss them in the context of observed mutation frequencies in global sequence datasets.

          Abstract

          The evolution of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been characterized by the emergence of mutations and so-called variants of concern that impact virus characteristics, including transmissibility and antigenicity. In this Review, members of the COVID-19 Genomics UK (COG-UK) Consortium and colleagues summarize mutations of the SARS-CoV-2 spike protein, focusing on their impacts on antigenicity and contextualizing them in the protein structure, and discuss them in the context of observed mutation frequencies in global sequence datasets.

          Related collections

          Most cited references88

          • Record: found
          • Abstract: found
          • Article: not found

          Structure of the SARS-CoV-2 spike receptor-binding domain bound to the ACE2 receptor

          A new and highly pathogenic coronavirus (severe acute respiratory syndrome coronavirus-2, SARS-CoV-2) caused an outbreak in Wuhan city, Hubei province, China, starting from December 2019 that quickly spread nationwide and to other countries around the world1-3. Here, to better understand the initial step of infection at an atomic level, we determined the crystal structure of the receptor-binding domain (RBD) of the spike protein of SARS-CoV-2 bound to the cell receptor ACE2. The overall ACE2-binding mode of the SARS-CoV-2 RBD is nearly identical to that of the SARS-CoV RBD, which also uses ACE2 as the cell receptor4. Structural analysis identified residues in the SARS-CoV-2 RBD that are essential for ACE2 binding, the majority of which either are highly conserved or share similar side chain properties with those in the SARS-CoV RBD. Such similarity in structure and sequence strongly indicate convergent evolution between the SARS-CoV-2 and SARS-CoV RBDs for improved binding to ACE2, although SARS-CoV-2 does not cluster within SARS and SARS-related coronaviruses1-3,5. The epitopes of two SARS-CoV antibodies that target the RBD are also analysed for binding to the SARS-CoV-2 RBD, providing insights into the future identification of cross-reactive antibodies.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            Tracking changes in SARS-CoV-2 Spike: evidence that D614G increases infectivity of the COVID-19 virus

            Summary A SARS-CoV-2 variant carrying the Spike protein amino acid change D614G has become the most prevalent form in the global pandemic. Dynamic tracking of variant frequencies revealed a recurrent pattern of G614 increase at multiple geographic levels: national, regional and municipal. The shift occurred even in local epidemics where the original D614 form was well established prior to the introduction of the G614 variant. The consistency of this pattern was highly statistically significant, suggesting that the G614 variant may have a fitness advantage. We found that the G614 variant grows to higher titer as pseudotyped virions. In infected individuals G614 is associated with lower RT-PCR cycle thresholds, suggestive of higher upper respiratory tract viral loads, although not with increased disease severity. These findings illuminate changes important for a mechanistic understanding of the virus, and support continuing surveillance of Spike mutations to aid in the development of immunological interventions.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses

              Over the past 20 years, several coronaviruses have crossed the species barrier into humans, causing outbreaks of severe, and often fatal, respiratory illness. Since SARS-CoV was first identified in animal markets, global viromics projects have discovered thousands of coronavirus sequences in diverse animals and geographic regions. Unfortunately, there are few tools available to functionally test these viruses for their ability to infect humans, which has severely hampered efforts to predict the next zoonotic viral outbreak. Here, we developed an approach to rapidly screen lineage B betacoronaviruses, such as SARS-CoV and the recent SARS-CoV-2, for receptor usage and their ability to infect cell types from different species. We show that host protease processing during viral entry is a significant barrier for several lineage B viruses and that bypassing this barrier allows several lineage B viruses to enter human cells through an unknown receptor. We also demonstrate how different lineage B viruses can recombine to gain entry into human cells, and confirm that human ACE2 is the receptor for the recently emerging SARS-CoV-2.
                Bookmark

                Author and article information

                Contributors
                david.l.robertson@glasgow.ac.uk
                Journal
                Nat Rev Microbiol
                Nat Rev Microbiol
                Nature Reviews. Microbiology
                Nature Publishing Group UK (London )
                1740-1526
                1740-1534
                1 June 2021
                : 1-16
                Affiliations
                [1 ]GRID grid.8756.c, ISNI 0000 0001 2193 314X, Institute of Biodiversity, Animal Health and Comparative Medicine, College of Medical, Veterinary and Life Sciences, , University of Glasgow, ; Glasgow, UK
                [2 ]GRID grid.301713.7, ISNI 0000 0004 0393 3981, MRC–University of Glasgow Centre for Virus Research, ; Glasgow, UK
                [3 ]GRID grid.5335.0, ISNI 0000000121885934, Department of Medicine, , University of Cambridge, ; Cambridge, UK
                [4 ]GRID grid.4305.2, ISNI 0000 0004 1936 7988, Institute of Evolutionary Biology, , University of Edinburgh, ; Edinburgh, UK
                [5 ]GRID grid.5335.0, ISNI 0000000121885934, Cambridge Institute of Therapeutic Immunology and Infectious Disease, , University of Cambridge, ; Cambridge, UK
                [6 ]GRID grid.8991.9, ISNI 0000 0004 0425 469X, Department of Clinical Research, , London School of Hygiene and Tropical Medicine, ; London, UK
                [7 ]GRID grid.10306.34, ISNI 0000 0004 0606 5382, Wellcome Sanger Institute, ; Hinxton, UK
                Author information
                http://orcid.org/0000-0001-9529-1127
                http://orcid.org/0000-0003-3625-4021
                http://orcid.org/0000-0002-9981-0649
                http://orcid.org/0000-0003-2589-8091
                http://orcid.org/0000-0003-4337-3707
                http://orcid.org/0000-0001-6338-0221
                Article
                573
                10.1038/s41579-021-00573-0
                8167834
                34075212
                ba934cd4-1f4b-4c66-ae96-2f892f745d63
                © Springer Nature Limited 2021

                This article is made available via the PMC Open Access Subset for unrestricted research re-use and secondary analysis in any form or by any means with acknowledgement of the original source. These permissions are granted for the duration of the World Health Organization (WHO) declaration of COVID-19 as a global pandemic.

                History
                : 30 April 2021
                Categories
                Review Article

                viral infection,protein analysis,vaccines,sars-cov-2,viral evolution

                Comments

                Comment on this article