Vir Biotechnology Publishes New Research Characterizing Variation in the SARS-CoV-2 Spike Protein and Virulence of a Prevalent Immune Evasion Variant, N439K

– Manuscript highlights the importance of molecular surveillance of SARS-CoV-2 immune evasion and rational design of vaccines and antibody therapies for COVID-19 –

SAN FRANCISCO, Nov. 06, 2020 (GLOBE NEWSWIRE) -- Vir Biotechnology, Inc. (Nasdaq: VIR) today announced the publication of new research demonstrating that the immunodominant SARS-CoV-2 receptor binding motif (RBM) 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. 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, which was developed by Vir in collaboration with the MRC-University of Glasgow Centre for Virus Research, was published online November 5, 2020 on bioRxiv, and has been submitted to a peer-reviewed journal for future print publication.  

“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,” said Herbert “Skip” Virgin, M.D., Ph.D., chief scientific officer of Vir. “It is reminiscent of our experience with influenza A, where the mutability of the region targeted by the most potent neutralizing antibodies results in ineffective immunity year-over-year. Our demonstration of a virulent SARS-CoV-2 immune evasion mutant provides a cautionary tale for how we address this pandemic, and indicates the importance of ongoing surveillance for immune evasion mutations in the development of antibodies and vaccines.”

Data analyzed from approximately 130,000 SARS-CoV-2 genomic sequences, alongside evaluation of a published deep mutational scanning of the receptor binding domain (RBD), demonstrated that the RBM has a high degree of structural plasticity that permits significant changes in the amino acid sequence of the RBM, including N439K, while maintaining hACE2 binding.

Researchers also sought to define the clinical and epidemiologic impact, molecular features and immune response to the RBM variant, N439K. The goal was to determine if variants emerging in the pandemic have immune evasion potential. This variant, which was first identified in Scotland in March 2020, has since re-emerged independently in a second lineage and has been observed in 14 countries, including the United States. At the time of manuscript submission, it was the second most common circulating RBD variant.