Abstract:
The coronavirus disease 2019 virus outbreak continues worldwide, with many
variants emerging, some of which are considered variants of concern (VOCs). The
WHO designated Omicron as a VOC and assigned it under variant B.1.1.529. Here,
we used computational studies to examine the VOCs, including Omicron
subvariants, and one variant of interest. Here we found that the binding affinity
of human receptor angiotensin‐converting enzyme 2 (hACE2) and receptor‐binding
domain (RBDs) increased in the order of wild type (Wuhan‐strain) < Beta
< Alpha < OmicronBA.5 < Gamma < Delta < Omicron BA.2.75 < BA.1 < BA.3 < BA.2.
Interactions between docked complexes revealed that the RBD residue positions
like 452, 478, 493, 498, 501, and 505 are crucial in creating strong interactions
with hACE2. Omicron BA.2 shows the highest binding capacity to the hACE2
receptor among all the mutant complexes. The BA.5's L452R, F486V, and T478K
mutation significantly impact the interaction network in the BA.5 RBD‐hACE2
interface. Here for the first time, we report the His505, an active residue on the
RBD forming a salt bridge in the BA.2, leading to increased mutation stability.
When the active RBD residues are mutated, binding affinity and intermolecular
interactions increase across all mutant complexes. By examining the differences in
different variants, this study may provide a solid foundation for structure‐based
drug design for newly emerging variants.
