SARS-CoV-2 Spike Variant Maintains Fitness While Evading Antibody-Mediated Immunity

New research was published demonstrating that the immunodominant SARS-CoV-2 receptor binding motif is the least conserved region in the SARS-CoV-2 spike protein, allowing for the occurrence of mutations without disrupting human ACE2 (hACE2) binding, which mediates viral entry.

These researchers also characterize the virulence and fitness of N439K, a prevalent variant in the RBM that demonstrated resistance to human neutralizing monoclonal antibodies (mAbs), including one that is currently being evaluated in clinical trials.

The manuscript was developed by Vir Bio, in collaboration with the MRC-University of Glasgow Centre for Virus Research, which was published online on November 5, 2020, and has been submitted to a peer-reviewed journal for future print publication.

Vir Bio's VIR-7831 (GSK4182136) is conducting a phase 2/3 study. This antibody is a fully human anti-SARS-CoV-2 monoclonal antibody that was selected based on its potential to neutralize the virus in vitro, kill infected cells, provide a high barrier to resistance, and achieve high concentrations in the lungs (one of the major sites of infection).

“This study shows that the receptor-binding motif of SARS-CoV-2, a major target of neutralizing antibodies, is evolving at a higher rate than the rest of the receptor-binding domain and spike, and is resilient to change,” stated Herbert “Skip” Virgin, M.D., Ph.D., chief scientific officer of Vir, in a press release.