High-throughput virtual screening of Streptomyces spp. metabolites as antiviral inhibitors against the Nipah virus matrix protein.

Autor: Macalalad MAB; Virology and Vaccine Research and Development Program, Department of Science and Technology - Industrial Technology Development Institute, Taguig 1631, Metro Manila, Philippines., Odchimar NMO; Virology and Vaccine Research and Development Program, Department of Science and Technology - Industrial Technology Development Institute, Taguig 1631, Metro Manila, Philippines., Orosco FL; Virology and Vaccine Research and Development Program, Department of Science and Technology - Industrial Technology Development Institute, Taguig 1631, Metro Manila, Philippines; S&T Fellows Program, Department of Science and Technology, Taguig 1631, Metro Manila, Philippines; Department of Biology, College of Arts and Sciences, University of the Philippines - Manila, Manila 1000, Metro Manila, Philippines. Electronic address: orosco.fredmoore@gmail.com.
Jazyk: angličtina
Zdroj: Computational biology and chemistry [Comput Biol Chem] 2024 Oct; Vol. 112, pp. 108133. Date of Electronic Publication: 2024 Jun 25.
DOI: 10.1016/j.compbiolchem.2024.108133
Abstrakt: Nipah virus (NiV) remains a significant global concern due to its impact on both the agricultural industry and human health, resulting in substantial economic and health consequences. Currently, there is no cure or commercially available vaccine for the virus. Therefore, it is crucial to prioritize the discovery of new and effective treatment options to prevent its continued spread. Streptomyces spp. are rich sources of metabolites known for their bioactivity against certain diseases; however, their potential as antiviral drugs against the Nipah virus remain unexplored. In this study, 6524 Streptomyces spp. metabolites were screened through in silico methods for their inhibitory effects against the Nipah virus matrix (NiV-M) protein, which assists in virion assembly of Nipah virus. Different computer-aided tools were utilized to carry out the virtual screening process: ADMET profiling revealed 913 compounds with excellent safety and efficacy profiles, molecular docking predicted the binding poses and associated docking scores of the ligands in their respective targets, MD simulations confirmed the binding stability of the top ten highest-scoring ligands in a 100 ns all-atom simulation, PCA elucidated simulation convergence, and MMPB(GB)SA calculations estimated the binding energies of the final candidate compounds and determined the key residues crucial for complex formation. Using in silico methods, we identified six metabolites targeting the main substrate-binding site and five targeting the dimerization site that exhibited excellent stability and strong binding affinity. We recommend testing these compounds in the next stages of drug development to confirm their effectiveness as therapeutic agents against Nipah virus.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this article.
(Copyright © 2024 Elsevier Ltd. All rights reserved.)
Databáze: MEDLINE
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