Mutations in SARS-CoV-2 spike protein receptor-binding domains may result in escape variants resistant to therapeutics and vaccines

All viruses mutate as they evolve, and most mutations have either negative or neutral effects on viral fitness. However, some mutations give viruses a selective advantage, making them more infectious, transmittable, and resistant to antibody responses and therapeutics. To better understand the relationship between immune responses to SARS-CoV-2 virus and how mutations may allow the virus to escape neutralization, researchers conducted a review of the literature, comprising approximately 139 studies. They synthesized research on emerging SARS-CoV-2 variants, described the structural basis of how antibodies may neutralize SARS-CoV-2, and mapped out the spike protein mutations or "escape variants" that resist antibody binding and neutralization.

The researchers summarized the structure-based classification of the spike protein receptor-binding domains (RBD) that target antibodies to better understand the molecular mechanisms of neutralization. They also further described the RBD escape mutations for several antibodies that resist vaccine-elicited and therapeutically relevant antibodies binding. Future studies are needed, however, to better understand how these mutations may affect illness severity and mortality.

According to the authors, "The potency of therapeutic antibodies and vaccines partly depends on how readily the virus can escape neutralization. The SARS-CoV-2 virus will continue to evolve resulting in the emergence of escape variants; therefore, worldwide genomic surveillance, better vaccination drive, development of broadly neutralizing antibodies, and new drugs are vital to combat COVID-19."

Mittal adds, "Structure-based escape maps combined with computational modelling are valuable tools to understand how mutations at each residue affect the binding of an antibody, and can be utilized to facilitate the rational design of escape-resistant antibody therapeutics, vaccines and other countermeasures."