tetano
Editor, Senior Moderator
J Med Virol
. 2022 Dec 15.
doi: 10.1002/jmv.28406. Online ahead of print.
In silico study of SARS-CoV-2 Spike protein RBD and human ACE-2 affinity dynamics across variants and Omicron sub-variants
Shamali Abeywardhana[SUP] 1 [/SUP], Upeka Bandaranayake[SUP] 2 [/SUP], Deshan B Perera[SUP] 3 [/SUP], Malinda Premathilaka[SUP] 4 [/SUP], Dinithi C Peiris[SUP] 5 [/SUP]
Affiliations
Abstract
The coronavirus disease 2019 (COVID-19) 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. We used computational studies to examine the VOCs Omicron sub-variants (OSVs) and one variant of interest (VOI) in this study. Here we found that the binding affinity of human receptor angiotensin-converting enzyme 2 (hACE2) and 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. This article is protected by copyright. All rights reserved.
Keywords: ACE-2 receptor; Omicron BA.5; RBD; SARS CoV-2; molecular dynamic (MD) simulation; protein-protein docking.
. 2022 Dec 15.
doi: 10.1002/jmv.28406. Online ahead of print.
In silico study of SARS-CoV-2 Spike protein RBD and human ACE-2 affinity dynamics across variants and Omicron sub-variants
Shamali Abeywardhana[SUP] 1 [/SUP], Upeka Bandaranayake[SUP] 2 [/SUP], Deshan B Perera[SUP] 3 [/SUP], Malinda Premathilaka[SUP] 4 [/SUP], Dinithi C Peiris[SUP] 5 [/SUP]
Affiliations
- PMID: 36519577
- DOI: 10.1002/jmv.28406
Abstract
The coronavirus disease 2019 (COVID-19) 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. We used computational studies to examine the VOCs Omicron sub-variants (OSVs) and one variant of interest (VOI) in this study. Here we found that the binding affinity of human receptor angiotensin-converting enzyme 2 (hACE2) and 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. This article is protected by copyright. All rights reserved.
Keywords: ACE-2 receptor; Omicron BA.5; RBD; SARS CoV-2; molecular dynamic (MD) simulation; protein-protein docking.