Structural basis for potent neutralization of SARS-CoV-2 and role of antibody affinity maturation.

Hurlburt, Nicholas K; Seydoux, Emilie; Wan, Yu-Hsin; Edara, Venkata Viswanadh; Stuart, Andrew B; Feng, Junli; Suthar, Mehul S; McGuire, Andrew T et al. · Nat Commun · 2020

basic_science · Level V

Where this comes from

Abstract

SARS-CoV-2 is a betacoronavirus virus responsible for the COVID-19 pandemic. Here, we determine the X-ray crystal structure of a potent neutralizing monoclonal antibody, CV30, isolated from a patient infected with SARS-CoV-2, in complex with the receptor binding domain. The structure reveals that CV30 binds to an epitope that overlaps with the human ACE2 receptor binding motif providing a structural basis for its neutralization. CV30 also induces shedding of the S1 subunit, indicating an additional mechanism of neutralization. A germline reversion of CV30 results in a substantial reduction in both binding affinity and neutralization potential indicating the minimal somatic mutation is needed for potently neutralizing antibodies against SARS-CoV-2.

Medical subject headings