Computational Investigation on the Physiochemical, Structural, and Binding Features of BA.2.75 and BA.2.75.2 Omicron Variants of SARS-CoV-2

Recently, several Omicron variants, including BA.2.75 and its sub-lineage BA.2.75.2, have demonstrated even better immune evasion and are responsible for waves of infections across the globe. BA.2.75 has been found in at least 15 nations and has become more prevalent in India. Additionally, BA.2.75.2 has expanded quickly, and it carries additional mutations R346T, F486S, and D1199N, suggesting a more extensive escape from neutralizing antibodies. This study analyzed physiochemical and structural characteristics of the spike protein (S protein) of BA.2.75 and BA.2.75.2 variants by employing various online tools, Molecular dynamics, and other computational approaches. The mutations G446S, R493Q, Q498R, N501Y, and N505H present in the RBD region of S protein of BA.2.75 and BA.2.75.2 were found to play a significant role in the binding of RBD of spike to ACE2. From the RMSD, RMSF, and inter-molecular hydrogen bond analyses, we found the S protein (BA.2.75)-ACE2 complex to have enhanced stability than the S protein (BA.2.75.2)-ACE2 complex. Also, we found the binding free energy value for the S (BA.2.75) -ACE2 complex (GBTOT= -20.03kcal/mol) to be relatively higher than the S (BA.2.75.2) -ACE2 complex (GBTOT= -15.19kcal/mol). The overall stability of the S protein (BA.2.75)-ACE2 complex may result in higher virulence of the strain.