PT  - JOURNAL ARTICLE
AU  - Meng Yuan
AU  - Deli Huang
AU  - Chang-Chun D. Lee
AU  - Nicholas C. Wu
AU  - Abigail M. Jackson
AU  - Xueyong Zhu
AU  - Hejun Liu
AU  - Linghang Peng
AU  - Marit J. van Gils
AU  - Rogier W. Sanders
AU  - Dennis R. Burton
AU  - S. Momsen Reincke
AU  - Harald Prüss
AU  - Jakob Kreye
AU  - David Nemazee
AU  - Andrew B. Ward
AU  - Ian A. Wilson
TI  - Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants
AID  - 10.1101/2021.02.16.430500
DP  - 2021 Jan 01
TA  - bioRxiv
PG  - 2021.02.16.430500
4099  - http://biorxiv.org/content/early/2021/02/17/2021.02.16.430500.short
4100  - http://biorxiv.org/content/early/2021/02/17/2021.02.16.430500.full
AB  - 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.Competing Interest StatementRelated to this work, the German Center for Neurodegenerative Diseases (DZNE) and Charite - Universitatsmedizin Berlin have filed a patent application that included the anti-SARS-CoV-2 antibody CV05-163.