Abstract
The scientific community has been releasing whole genomic sequences of SARS-CoV-2 to facilitate the investigation of molecular features and evolutionary history. We retrieved 36 genomes of 18 prevalent countries of Asia, Europe and America for genomic diversity and mutational analysis. Besides, we studied mutations in the RBD regions of Spike (S) proteins to analyze the drug efficiency against these mutations. In this research, phylogenenetic analysis, evolutionary modeling, substitution pattern analysis, molecular docking, dynamics simulation, etc. were performed. The genomic sequences showed >99% similarity with the reference sequence of China.TN93 + G was predicted as a best nucleotide substitution model. It was revealed that effective transition from the co-existing SARS genome to the SARS-CoV-2 and a noticeable positive selection in the SARS-CoV-2 genomes occurred. Moreover, three mutations in RBD domain, Val/ Phe367, Val/ Leu 382 and Ala/ Val522, were discovered in the genomes from Netherland, Bangladesh and the USA, respectively. Molecular docking and dynamics study showed RBD with mutation Val/Leu382 had the lowest binding affinity with remdesivir. In conclusion, the SARS-CoV-2 genomes are similar, but multiple degrees of transitions and transversions occurred. The mutations cause a significant conformational change, which are needed to be investigated during drug and vaccine development.
Keywords: Molecular dynamics simulation; Mutational analysis; Phylogenomic diversity; Remdesivir; S protein; SARS-CoV-2.
【저자키워드】 SARS-CoV-2, S protein, Remdesivir, Molecular dynamics simulation, mutational analysis, Phylogenomic diversity, 【초록키워드】 SARS-CoV-2, Vaccine development, Europe, Mutation, S protein, spike, Positive selection, Genome, mutations, molecular docking, Remdesivir, docking, molecular dynamics, binding affinity, Molecular dynamics simulation, Asia, Protein, Region, RBD, Research, Scientific community, genomes, USA, genomic, drug and vaccine development, reference sequence, nucleotide, Analysis, conformational change, similarity, Efficiency, RBD domain, SARS-CoV-2 genomes, America, molecular features, nucleotide substitution, genomic sequence, country, effective, prevalent, lowest, predicted, performed, occurred, investigated, facilitate, the RBD, molecular feature, retrieved, the SARS-CoV-2, the SARS-CoV-2 genome, 【제목키워드】 SARS-CoV-2, inactivation, molecular, Interaction, domain,