Genomic diversity and molecular dynamics interaction on mutational variances among RB domains of SARS-CoV-2 interplay drug inactivation

Md Bashir Uddin, Emran Hossain Sajib, Syeda Farjana Hoque, Md Nazmul Islam Bappy, Fazle Elahi, Arabinda Ghosh, Samuel Muhit, Mohammad Mahmudul Hassan, Mahmudul Hasan, Ramachandran Chelliah, Se Jin Park, Tamanna Jahan Mony, Deog Hwan Oh, Syed Sayeem Uddin Ahmed

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

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.

Original languageEnglish (US)
Article number105128
JournalInfection, Genetics and Evolution
Volume97
DOIs
StatePublished - Jan 2022

Keywords

  • Molecular dynamics simulation
  • Mutational analysis
  • Phylogenomic diversity
  • Remdesivir
  • S protein
  • SARS-CoV-2

ASJC Scopus subject areas

  • Microbiology
  • Ecology, Evolution, Behavior and Systematics
  • Molecular Biology
  • Genetics
  • Microbiology (medical)
  • Infectious Diseases

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