Mutation Pattern in the Receptor Binding Motif of SARS-Cov-2 Variants and the Effect on Molecular Interactions in Docked Ligand Complexes

Abstract

The spike glycoprotein of SARS-Cov-2 is a therapeutic target for Covid-19 and mutations in the Receptor Binding Motif (RBM) may alter the binding properties of ligands proposed to inhibit viral entry. This study aimed to identify the existence of a mutation pattern in the RBMs of SARS-Cov-2 variants and study the effect on ligand binding interactions. RBM sequences were obtained using NCBI BLASTP and subjected to multiple and pairwise sequence alignment analysis. Hypothetical generations were drawn from the phylogenetic tree. The effect of mutation on ligand binding was studied by docking zafirlukast on selected RBMs. Molecular dynamics simulations were conducted to explain molecular interactions. The sequences at the same phylogenetic level showed higher similarity with the observed differences defined by the crystallized chain length. 6XDG_E, a leaf node sequence was 76% similar to 7NXA_E, a branch from the root, and had the highest mutation. Differences in sequence similarity across successive generations were based on mutations and crystallized chain length and the amino acid substitution is not predictable. Different bond types and binding affinities were observed as well as varying Root Mean Square Deviation (RMSD), Root Mean Square Fluctuation (RMSF), and Region of Gyration (RoG) values for the RBMs in different variants. The RMSD, RMSF, and RoG did not differ significantly in the bound and free states of RBM from specific variants suggesting that the observed differences are attributable to amino acid substitutions. This information is crucial for drug development intended to block SARS-Cov-2 entry.

Evaluation of the Antioxidant Properties of Carvacrol as a Prospective Replacement for Crude Essential Oils and Synthetic Antioxidants in Food Storage

“…The molecular dynamics production was run at 200 ns of NPT (constant number N, pressure P, and temperature T), where equilibration of the system was reached at 300 K for another 2 ns at a pressure of 1 bar. After molecular dynamics simulation, the PTRAJ and CPPTRAJ modules in AMBER 14 were used to analyse root-mean-square deviation (RMSD), root-mean-square fluctuations (RMSF) and region of gyration (RoG) [ 40 ].…”