Antibody targeting of conserved sites of vulnerability on the SARS-CoV-2 spike receptor-binding domain.

Publication date: Feb 01, 2024

Given the continuous emergence of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variants of concern (VoCs), immunotherapeutics that target conserved epitopes on the spike (S) glycoprotein have therapeutic advantages. Here, we report the crystal structure of the SARS-CoV-2 S receptor-binding domain (RBD) at 1. 95 A and describe flexibility and distinct conformations of the angiotensin-converting enzyme 2 (ACE2)-binding site. We identify a set of SARS-CoV-2-reactive monoclonal antibodies (mAbs) with broad RBD cross-reactivity including SARS-CoV-2 Omicron subvariants, SARS-CoV-1, and other sarbecoviruses and determine the crystal structures of mAb-RBD complexes with Ab246 and CR3022 mAbs targeting the class IV site, WRAIR-2134, which binds the recently designated class V epitope, and WRAIR-2123, the class I ACE2-binding site. The broad reactivity of class IV and V mAbs to conserved regions of SARS-CoV-2 VoCs and other sarbecovirus provides a framework for long-term immunotherapeutic development strategies.

Concepts Keywords
Antibody Ace2
Immunotherapeutic Binding
Sarbecoviruses Class
Conserved
Cov
Crystal
Domain
Mabs
Rbd
Receptor
Sars
Site
Spike
Targeting
Vocs

Semantics

Type Source Name
disease VO Severe acute respiratory syndrome coronavirus 2
disease VO Glycoprotein
disease VO report
drug DRUGBANK Angiotensin II
disease IDO site

Original Article

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