Journal Article

DZNE-2021-01477

http://join2-wiki.gsi.de/foswiki/pub/Main/Artwork/join2_logo100x88.png Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants.

Yuan, M. ; Huang, D. ; Lee, C. D. ; Wu, N. C. ; Jackson, A. M. ; Zhu, X. ; Liu, H. ; Peng, L. ; van Gils, M. J. ; Sanders, R. W. ; Burton, D. R. ; Reincke, M.DZNE* ; Prüß, H.DZNE* ; Kreye, J.DZNE* ; Nemazee, D. ; Ward, A. B. ; Wilson, I. A.

2021
Moses King Cambridge, Mass.

This record in other databases:    

Please use a persistent id in citations: doi:10.1126/science.abh1139

Abstract: Neutralizing antibodies (nAbs) elicited against the receptor binding site (RBS) of the spike protein of wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are generally less effective against recent variants of concern. RBS residues Glu484, Lys417, and Asn501 are mutated in variants first described in South Africa (B.1.351) and Brazil (P.1). We analyzed their effects on angiotensin-converting enzyme 2 binding, as well as the effects of two of these mutations (K417N and E484K) on nAbs isolated from COVID-19 patients. Binding and neutralization of the two most frequently elicited antibody families (IGHV3-53/3-66 and IGHV1-2), which can both bind the RBS in alternative binding modes, are abrogated by K417N, E484K, or both. These effects can be structurally explained by their extensive interactions with RBS nAbs. However, nAbs to the more conserved, cross-neutralizing CR3022 and S309 sites were largely unaffected. The results have implications for next-generation vaccines and antibody therapies.

Keyword(s): Angiotensin-Converting Enzyme 2: metabolism (MeSH) ; Antibodies, Neutralizing: immunology (MeSH) ; Antibodies, Neutralizing: metabolism (MeSH) ; Antibodies, Viral: immunology (MeSH) ; Antibodies, Viral: metabolism (MeSH) ; Antigenic Variation (MeSH) ; Antigens, Viral: chemistry (MeSH) ; Antigens, Viral: genetics (MeSH) ; Antigens, Viral: immunology (MeSH) ; Antigens, Viral: metabolism (MeSH) ; Binding Sites (MeSH) ; Binding Sites, Antibody (MeSH) ; COVID-19: immunology (MeSH) ; COVID-19: virology (MeSH) ; Epitopes (MeSH) ; Humans (MeSH) ; Immune Evasion (MeSH) ; Mutation (MeSH) ; Protein Binding (MeSH) ; Protein Domains (MeSH) ; Receptors, Coronavirus: metabolism (MeSH) ; SARS-CoV-2: chemistry (MeSH) ; SARS-CoV-2: genetics (MeSH) ; SARS-CoV-2: immunology (MeSH) ; Spike Glycoprotein, Coronavirus: chemistry (MeSH) ; Spike Glycoprotein, Coronavirus: genetics (MeSH) ; Spike Glycoprotein, Coronavirus: immunology (MeSH) ; Spike Glycoprotein, Coronavirus: metabolism (MeSH) ; Antibodies, Neutralizing ; Antibodies, Viral ; Antigens, Viral ; Epitopes ; Receptors, Coronavirus ; Spike Glycoprotein, Coronavirus ; spike protein, SARS-CoV-2 ; ACE2 protein, human ; Angiotensin-Converting Enzyme 2

Note: ISSN 1095-9203 not unique: **3 hits**.

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Contributing Institute(s):

1. Autoimmune Enzephalopathies (AG Prüß)

Research Program(s):

1. 353 - Clinical and Health Care Research (POF4-353) (POF4-353)

Appears in the scientific report 2021

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Database coverage:
; BIOSIS Previews ; Biological Abstracts ; Chemical Reactions ; Clarivate Analytics Master Journal List ; Current Contents - Agriculture, Biology and Environmental Sciences ; Current Contents - Life Sciences ; Current Contents - Physical, Chemical and Earth Sciences ; Ebsco Academic Search ; Essential Science Indicators ; IF >= 60 ; Index Chemicus ; JCR ; National-Konsortium ; SCOPUS ; Science Citation Index Expanded ; Web of Science Core Collection ; Zoological Record

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