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

Autor: Mahmudul Hasan, Tamanna Jahan Mony, Arabinda Ghosh, Nazmul Islam Bappy, Bashir Uddin, Samuel Muhit, Emran Hossain Sajib, Syed Sayeem Uddin Ahmed, Mohammad Mahmudul Hassan, Ramachandran Chelliah, Fazle Elahi, Deog-Hwan Oh, Se Jin Park, Syeda Farjana Hoque
Rok vydání: 2021
Předmět:
Protein Conformation
alpha-Helical
Conformational change
Gene Expression
medicine.disease_cause
Genome
Molecular dynamics
Phylogeny
media_common
Netherlands
Genetics
Mutation
Bangladesh
Likelihood Functions
Alanine
Transition (genetics)
Molecular Docking Simulation
Infectious Diseases
Spike Glycoprotein
Coronavirus
Protein Binding
Research Paper
Microbiology (medical)
Drug
China
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)
media_common.quotation_subject
Remdesivir
Genome
Viral
Biology
Molecular Dynamics Simulation
Microbiology
Antiviral Agents
Evolution
Molecular
S protein
medicine
Humans
Protein Interaction Domains and Motifs
Molecular Biology
Ecology
Evolution
Behavior and Systematics
Binding Sites
SARS-CoV-2
COVID-19
Phylogenomic diversity
Mutational analysis
Adenosine Monophosphate
United States
COVID-19 Drug Treatment
Amino Acid Substitution
Protein Conformation
beta-Strand
Reference genome
Zdroj: Infection, Genetics and Evolution
ISSN: 1567-7257
Popis: 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.
Databáze: OpenAIRE
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