Study on Sequence Mutation and Molecular Dynamics Simulation of D614G SARS-CoV-2 Spike Protein in Indonesia

Abstract

Amino acid mutations in the D614G spike protein of SARS-CoV-2 need to be studied more deeply for their influence on the pathogenesis of the virus. The purpose of this research was to analyze 1) the variation and kinship of the SARS-CoV-2 spike protein gene; 2) the effect of D614G spike protein mutation on ACE2 receptor binding and the molecular dynamics simulation. The nucleotide sequence of SARS-CoV-2 virus isolate was downloaded from GISAID and NCBI. Classification of SARS-CoV-2 clades and construction of the phylogenetic tree using MEGA-program. Molecular dynamics simulation was demonstrated with GROMACS to compare the stability of D614 and G614 S proteins. The result of this research showed that the most common GH clade SARS-CoV-2 virus isolates were be discovered in Indonesia, and the percentage of isolates with the D614G mutation reached 97% in Indonesia. The clade with the D614G mutation made the SARS-CoV-2 virus more varied with new mutations and increased human-to-human transmision. In this study, an increase in infectivity or spread of the SARS-CoV-2 D614G virus most likely resulted from an increase in the strength of the S protein and a slight change in RBD conformation seen from the molecular interactions around the mutation area and the RMSF value (0.3144 nm for D614G, and 0.3818 nm for D614). This is likely to be the cause of the massive spread of variants belonging to VOC and VBM, where all these variants have the D614G mutation.