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TitleStructural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants.
Journal, issue, pagesbioRxiv, Year 2021
Publish dateFeb 17, 2021
AuthorsMeng Yuan / Deli Huang / Chang-Chun D Lee / Nicholas C Wu / Abigail M Jackson / Xueyong Zhu / Hejun Liu / Linghang Peng / Marit J van Gils / Rogier W Sanders / Dennis R Burton / S Momsen Reincke / Harald Prüss / Jakob Kreye / David Nemazee / Andrew B Ward / Ian A Wilson /
PubMed AbstractThe protective efficacy of neutralizing antibodies (nAbs) elicited during natural infection with SARS-CoV-2 and by vaccination based on its spike protein has been compromised with emergence of the ...The protective efficacy of neutralizing antibodies (nAbs) elicited during natural infection with SARS-CoV-2 and by vaccination based on its spike protein has been compromised with emergence of the recent SARS-CoV-2 variants. Residues E484 and K417 in the receptor-binding site (RBS) are both mutated in lineages first described in South Africa (B.1.351) and Brazil (B.1.1.28.1). The nAbs isolated from SARS-CoV-2 patients are preferentially encoded by certain heavy-chain germline genes and the two most frequently elicited antibody families (IGHV3-53/3-66 and IGHV1-2) can each bind the RBS in two different binding modes. However, their binding and neutralization are abrogated by either the E484K or K417N mutation, whereas nAbs to the cross-reactive CR3022 and S309 sites are largely unaffected. This structural and functional analysis illustrates why mutations at E484 and K417 adversely affect major classes of nAbs to SARS-CoV-2 with consequences for next-generation COVID-19 vaccines.
External linksbioRxiv / PubMed:33619487 / PubMed Central
MethodsEM (single particle)
Resolution25.0 Å
Structure data

EMDB-23466:
SARS-CoV-2-6P-Mut7 + CV05-163 Fab: 1 fab bound
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-23467:
SARS-CoV-2-6P-Mut7 + CV05-163 Fab: 2 fabs bound
Method: EM (single particle) / Resolution: 25.0 Å

EMDB-23468:
SARS-CoV-2-6P-Mut7 + CV05-163 Fab: 3 fabs bound
Method: EM (single particle) / Resolution: 25.0 Å

Source
  • Severe acute respiratory syndrome coronavirus 2
  • Homo sapiens (human)

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