The Effects of Mutations in SARS-CoV-2 Variants On Viral Infectivity

The SARS-CoV-2 virus is a positive strand RNA virus whose genome encodes four structural proteins including the spike protein. The Spike protein is a type I fusion protein responsible for receptor binding and membrane fusion. As a result of the emergence of new variants of SARS-CoV-2, we decided to investigate how the interactions between the different spike proteins of new variants and the human ACE2 receptor affect the infectivity of each virus, specifically researching the four variants of concern in the United States classified by the CDC: Alpha, Beta, Gamma, and Delta, variants. Stronger attraction between the ACE2 receptor and the variant’s spike protein increases infectivity, so we predicted that factors that influence the strength of attraction between the two structures would produce differently infectious variants and that these factors would be accurate measures of infectivity. To answer this, we downloaded the sequences of the spike proteins of concern from open access data sources including NCBI/RCSB. We then collected and analysed data on the differences between the spike proteins and their interactions with the ACE2 receptor using sequence alignment tool, Clustal Omega, and modeling tools on Chimera X. We determined the infectivity of a variant by analyzing: bond length, surface charge, isoelectricity, aromaticity, and amino acid substitutions. Early findings indicated that the Delta variant was the most infectious and that the studied molecular characteristics were correlated with the variant’s level of infectivity, where Delta resulted in most infective in ¾ studied areas. Extensions of this research project include finding which of the molecular properties is most significant in determining the infectivity of the variants, which could advance treatment and prevention methods for this virus which target this property .