Target specificity of selective bioactive compounds in blocking α-dystroglycan receptor to suppress Lassa virus infection: an in silico approach

Adittya Arefin, Tanzila Ismail Ema, Tamnia Islam, Md Saddam Hossen, Tariqul Islam, Salauddin Al Azad, Md Nasir Uddin Badal, Md Aminul Islam, Partha Biswas, Nafee Ul Alam, Enayetul Islam, Maliha Anjum, Afsana Masud, Md Shaikh Kamran, Ahsab Rahman, Parag Kumar Paul

Research output: Contribution to journalArticlepeer-review

1 Scopus citations

Abstract

Lassa hemorrhagic fever, caused by Lassa mammarenavirus (LASV) infection, accumulates up to 5000 deaths every year. Currently, there is no vaccine available to combat this disease. In this study, a library of 200 bioactive compounds was virtually screened to study their drug-likeness with the capacity to block the α-dystroglycan (α-DG) receptor and prevent LASV influx. Following rigorous absorption, distribution, metabolism, and excretion (ADME) and quantitative structure-activity relationship (QSAR) profiling, molecular docking was conducted with the top ligands against the α-DG receptor. The compounds chrysin, reticuline, and 3-caffeoylshikimic acid emerged as the top three ligands in terms of binding affinity. Post-docking analysis revealed that interactions with Arg76, Asn224, Ser259, and Lys302 amino acid residues of the receptor protein were important for the optimum binding affinity of ligands. Molecular dynamics simulation was performed comprehensively to study the stability of the protein-ligand complexes. In-depth assessment of root-mean-square deviation (RMSD), root mean square fluctuation (RMSF), polar surface area (PSA), B-Factor, radius of gyration (Rg), solvent accessible surface area (SASA), and molecular surface area (MolSA) values of the protein-ligand complexes affirmed that the candidates with the best binding affinity formed the most stable protein-ligand complexes. To authenticate the potentialities of the ligands as target-specific drugs, an in vivo study is underway in real time as the continuation of the research.

Original languageEnglish (US)
Pages (from-to)459-473
Number of pages15
JournalJournal of Biomedical Research
Volume35
Issue number6
DOIs
StatePublished - 2021
Externally publishedYes

Keywords

  • Bioactive compounds
  • Lasv infection
  • Molecular docking
  • Molecular dynamic simulations
  • Target specificity
  • Α-dystroglycan receptor

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

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