In silico study of SARS‐CoV‐2 spike protein RBD and human ACE‐2 affinity dynamics across variants and Omicron subvariants

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.

Potential differentiation of successive SARS-CoV-2 mutations by RNA: DNA hybrid analyses

“…During the SARS-CoV-2 pandemic, computational approaches effectively assist researchers to predict protein-protein interactions and screening possible drugs faster. Abeywardhana et al used computational studies to examine the binding affinity of ACE2 and several variants, they found that Omicron BA.2 shows the highest binding capacity to the ACE2 [ 23 ]. Mondeali et al studied the interactions of the S477N-ACE2 in silico and revealed an increased binding affinity of N477 for ACE2 [ 24 ].…”

The 249RWMD spike protein insertion in Omicron BQ.1 subvariant compensates the 24LPP and 69HV deletions and may cause severe disease than BF.7 and XBB.1 subvariants

“…Abeyardhana et al found that the binding a nity of ACE-2 receptor and RBD domain increased in the order of Wuhan < Beta < Alpha < BA.5 < Gamma < Delta < 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 were crucial in creating strong interactions with ACE-2 [25]. Omicron BA.2 shows the highest binding capacity to the ACE-2 receptor among all the mutant complexes studied.…”

“…Omicron BA.2 shows the highest binding capacity to the ACE-2 receptor among all the mutant complexes studied. The L452R, F486V, and T478K mutations in the spike of BA5 signi cantly impacted the interaction network in the BA.5 RBD-ACE2 interface [25].…”

Development and validation of a prognostic model based on immune variables to early predict severe cases of SARS-CoV-2 Omicron variant infection

“…Since December 2021, the SARS-CoV-2 Omicron variant has rapidly preempted the shares of other VOCs like the Delta and Gamma variants and become the predominant variant globally. The enhanced ability of the Omicron variant to evade vaccine or infection-induced immunity and bind with angiotensinconverting enzyme 2 receptor confers its exceedingly potent infectivity and high odds of reinfection and breakthrough infection (18,26,27). Moreover, more and more countries canceled their previously strict COVID-19 management, thus leading to a surge of infected cases.…”