Probing the binding nature and stability of highly transmissible mutated variant alpha to omicron of SARS‐CoV‐2 RBD with ACE2 via molecular dynamics simulation

Abstract

AbstractCurrently, no approved drug is available as a causative agent of coronavirus disease 2019 (COVID‐19) except for some repurposed drugs. The first structure of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) was reported in late 2019, based on that some vaccines and repurposed drugs were approved to prevent people from COVID‐19 during the pandemic situation. Since then, new types of variants emerged and notably, the receptor binding domain (RBD) adopted different binding modes with angiotensin‐converting enzyme 2 (ACE2); this made significant changes in the progression of COVID‐19. Some of the new variants are highly infectious spreading fast and dangerous. The present study is focused on understanding the binding mode of the RBD of different mutated SARS‐CoV‐2 variants of concern (alpha to omicron) with the human ACE2 using molecular dynamics simulation. Notably, some variants adopted a new binding mode of RBD with ACE2 and formed different interactions, which is unlike the wild type; this was confirmed from the comparison of interaction between RBD‐ACE2 of all variants with its wild‐type structure. Binding energy values confirm that some mutated variants exhibit high binding affinity. These findings demonstrate that the variations in the sequence of SARS‐CoV‐2 S‐protein altered the binding mode of RBD; this may be the reason that the virus has high transmissibility and causes new infections. This in‐silico study on mutated variants of SARS‐CoV‐2 RBD with ACE2 insights into their binding mode, binding affinity, and stability. This information may help to understand the RBD‐ACE2 binding domains, which allows for designing newer drugs and vaccines.