Abstract
Simple SummarySince the onset of the COVID-19 pandemic in late 2019, SARS-CoV-2 has evolved via genetic changes, resulting in numerous variants of concern (VOCs) and interest (VOIs). Using protein-protein docking and dynamics simulation, we examined the interactions of five SARS-CoV-2 variations’ receptor-binding domains with the human angiotensin-converting enzyme 2 (hACE2) receptor in host cells. A comparison of protein-protein docking and dynamics simulations showed that these point mutations significantly altered the structural behavior of the spike (S) protein, affecting RBD binding to hACE2 at the respective sites. Further research is needed to determine whether these changes affect drug–S protein binding and its potential therapeutic impact.Since the beginning of the coronavirus 19 (COVID-19) pandemic in late 2019, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been evolving through the acquisition of genomic mutations, leading to the emergence of multiple variants of concern (VOCs) and variants of interest (VOIs). Currently, four VOCs (Alpha, Beta, Delta, and Gamma) and seven VOIs (Epsilon, Zeta, Eta, Theta, Iota, Kappa, and Lambda) of SARS-CoV-2 have been identified in worldwide circulation. Here, we investigated the interactions of the receptor-binding domain (RBD) of five SARS-CoV-2 variants with the human angiotensin-converting enzyme 2 (hACE2) receptor in host cells, to determine the extent of molecular divergence and the impact of mutation, using protein-protein docking and dynamics simulation approaches. Along with the wild-type (WT) SARS-CoV-2, this study included the Brazilian (BR/lineage P.1/Gamma), Indian (IN/lineage B.1.617/Delta), South African (SA/lineage B.1.351/Beta), United Kingdom (UK/lineage B.1.1.7/Alpha), and United States (US/lineage B.1.429/Epsilon) variants. The protein-protein docking and dynamics simulation studies revealed that these point mutations considerably affected the structural behavior of the spike (S) protein compared to the WT, which also affected the binding of RBD with hACE2 at the respective sites. Additional experimental studies are required to determine whether these effects have an influence on drug–S protein binding and its potential therapeutic effect.
Highlights
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has had a major impact on human health and socioeconomic status globally [1,2]
The majority of variants created through alterations in amino acids in the receptor-binding domain (RBD) have been found to be less infectious [39], but certain variations investigated have been resistant to some neutralizing antibodies [40]
A mutation that occurred outside the RBD region (D614G) was reported to be more infectious, there was no evidence that this variant was resistant to neutralizing antibodies [39]
Summary
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which causes coronavirus disease 2019 (COVID-19), has had a major impact on human health and socioeconomic status globally [1,2]. SARS-CoV-2 is a single-stranded positive-sense RNA (+ssRNA) with a 29.9 kb genomic length and contains two large ORFs (ORF1a and ORF1b) which encode for 16 non-structural protein (nsp1-16) and structural protein encoding genes [3,4]. The virus consists of four structural proteins, namely spike (S), envelope (E), membrane (M), and nucleocapsid (N), among which the former three are integral membrane proteins and the latter remains complexed with its RNA genome. It comprises 9 or 10 accessory proteins [5,6,7]. The remaining genomic region preceding the 3 -UTR possesses four ORFs that encode S, E, M, and N structural proteins, as well as 9 or 10 interspersed ORFs that correspond to accessory proteins [8,9,10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
