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

Publication Type:

Journal Article

Source:

Structure (2023)

Abstract:

<p>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)&nbsp;glycoprotein have therapeutic advantages. Here, we report the crystal structure of the SARS-CoV-2&nbsp;S receptor-binding domain (RBD) at 1.95&nbsp;Å 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.</p>

PDB: 
8SGU , 6W7Y , 8FAH , 7U8E , 8SMT , 8SMI
Detector: 
EIGER
EIGER2
Beamline: 
24-ID-C
24-ID-E