Genetic and structural basis for recognition of SARS-CoV-2 spike protein by a two-antibody cocktail.

BioRxiv : the Preprint Server for Biology
Jinhui DongJames E Crowe

Abstract

The SARS-CoV-2 pandemic has led to an urgent need to understand the molecular basis for immune recognition of SARS-CoV-2 spike (S) glycoprotein antigenic sites. To define the genetic and structural basis for SARS-CoV-2 neutralization, we determined the structures of two human monoclonal antibodies COV2-2196 and COV2-2130 1 , which form the basis of the investigational antibody cocktail AZD7442, in complex with the receptor binding domain (RBD) of SARS-CoV-2. COV2-2196 forms an "aromatic cage" at the heavy/light chain interface using germline-encoded residues in complementarity determining regions (CDRs) 2 and 3 of the heavy chain and CDRs 1 and 3 of the light chain. These structural features explain why highly similar antibodies (public clonotypes) have been isolated from multiple individuals 1-4 . The structure of COV2-2130 reveals that an unusually long LCDR1 and HCDR3 make interactions with the opposite face of the RBD from that of COV2-2196. Using deep mutational scanning and neutralization escape selection experiments, we comprehensively mapped the critical residues of both antibodies and identified positions of concern for possible viral escape. Nonetheless, both COV2-2196 and COV2130 showed strong neutralizing activity a...Continue Reading

Citations

Mar 16, 2021·EFSA Journal·European Food Safety Authority and European Centre for Disease Prevention and ControlGrazina Mirinaviciute
Jun 3, 2021·Antioxidants·Alessio Danilo InchingoloFrancesco Inchingolo

Datasets Mentioned

BETA
PRJNA511481
PRJNA639956
..

Methods Mentioned

BETA
glycosylation
electron microscopy

Clinical Trials Mentioned

NCT04625972
NCT04625725
NCT04723394
NCT04518410
NCT04501978

Related Concepts

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