Interactions of the Receptor Binding Domain of SARS-CoV-2 Variants with hACE2: Insights from Molecular Docking Analysis and Molecular Dynamic Simulation

Abstract

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.

Insights into the Binding of Receptor-Binding Domain (RBD) of SARS-CoV-2 Wild Type and B.1.620 Variant with hACE2 Using Molecular Docking and Simulation Approaches

“…Similar findings are also reported by other studies on other variants [ 26 , 31 , 56 ]. However, similar docking results higher for the variants are reported in a recent report [ 16 ]. The docking scores, including the HADDOCK scores, vdW, electrostatic energy, and other parameters predicted by HADDOCK for both the complexes, are given in Table 1 .…”

“…Variations in different proteins of SARS-CoV-2, particularly the spike glycoprotein, lead to a drift in the antigenicity of vaccines or other therapeutics [ 12 , 13 , 14 , 15 ]. The US government’s SARS-CoV-2 Interagency Group (SIG) and the European Center for Disease Prevention and Control (ECDC) have classified SARS-CoV-2 variants into three groups, i.e., variants of concern (VOCs), variants of interest (VOIs), and variants of high consequence (VOHCs) [ 16 ]. Due to the phenomenal spread of VOCs, they remained a concern because of their enhanced transmission, causing more severe disease, a significant decline in antibody neutralization, and decreased treatment effectiveness [ 17 ].…”

Computational prediction of the effect of mutations in the receptor-binding domain on the interaction between SARS-CoV-2 and human ACE2

“…Until now, the US government's SARS-CoV-2 Interagency Group (SIG) and the European Center for Disease Prevention and Control (ECDC) have continued to monitor the development of the emergence of new variants of this virus. They have classified SARS-CoV-2 variants into three categories as follows: variants of interest (VOI), variants of concern (VOC), and variants of high consequence (VOHC) [1]. The rapid spread of VOCs has become one of the remaining concerns due to their increased transmissibility, the severity of disease, significant reduction in antibody neutralization, and decreased treatment effectiveness [2][3][4][5][6].…”

Fruit Bromelain-Derived Peptide Potentially Restrains the Attachment of SARS-CoV-2 Variants to hACE2: A Pharmacoinformatics Approach

“…Binding affinity is used to assess and rank the strength of the interactions formed, which is also calculated by the equilibrium dissociation constant. Thus, the lower the K D value, the higher the affinity [ 63 ]. The lowest K D value was obtained from the interaction of the bromelain-derived peptide with the NG variant (9.7 × 10 −8 M), followed by the US (1.8 × 10 −7 M), UK (2.4 × 10 −7 M), SC (2.7 × 10 −7 M), WT (3.3 × 10 −7 M), SG (3.5 × 10 −7 M), SN (4.7 × 10 −7 M), IN (5.1 × 10 −7 M), and SA (6.6 × 10 −7 M) variants.…”