Mapping the evolutionary space of SARS-CoV-2 variants to anticipate emergence of subvariants resistant to COVID-19 therapeutics

Abstract

New sublineages of SARS-CoV-2 variants-of-concern (VOCs) continuously emerge with mutations in the spike glycoprotein. In most cases, the sublineage-defining mutations vary between the VOCs. It is unclear whether these differences reflect lineage-specific likelihoods for mutations at each spike position or the stochastic nature of their appearance. We describe a systematic approach to identify clues that can predict the mutational profiles of SARS-CoV-2 subvariants at early stages after emergence of their parental lineages. This work provides a framework for anticipating the emergence of subvariants resistant to COVID-19 therapeutics by mapping the evolutionary space of SARS-CoV-2 variants.