From antibiotic to antiviral: computational screening reveals a multi-targeting antibiotic from Streptomyces spp. against Nipah virus fusion proteins.

Autor: Odchimar NMO; Virology and Vaccine Research and Development Program, Department of Science and Technology - Industrial Technology Development Institute, 1631, Taguig City, Metro Manila, Philippines., Macalalad MAB; Virology and Vaccine Research and Development Program, Department of Science and Technology - Industrial Technology Development Institute, 1631, Taguig City, Metro Manila, Philippines., Orosco FL; Virology and Vaccine Research and Development Program, Department of Science and Technology - Industrial Technology Development Institute, 1631, Taguig City, Metro Manila, Philippines. orosco.fredmoore@gmail.com.; S&T Fellows Program, Department of Science and Technology, 1631, Taguig City, Metro Manila, Philippines. orosco.fredmoore@gmail.com.; Department of Biology, College of Arts and Sciences, University of the Philippines - Manila, 1000, Manila, Metro Manila, Philippines. orosco.fredmoore@gmail.com.
Jazyk: angličtina
Zdroj: Molecular diversity [Mol Divers] 2024 Jul 26. Date of Electronic Publication: 2024 Jul 26.
DOI: 10.1007/s11030-024-10932-7
Abstrakt: Nipah Virus is a re-emerging zoonotic paramyxovirus that poses a significant threat to both swine industry and human health. The pursuit of potential antiviral agents with both preventive and therapeutic properties holds promise for targeting such viruses. To expedite this search, leveraging computational biology is essential. Streptomyces is renowned for its capacity to produce large and diverse metabolites with promising bioactivities. In the current study, we conducted a comprehensive structure-based virtual screening of 6524 Streptomyces spp. metabolites sourced from the StreptomeDB database to evaluate their potential inhibitory effects on three Nipah virus fusion (NiVF) protein conformations: NiVF pre-fusion 1-mer (NiVF-1mer), pre-fusion 3-mer (NiVF-3mer), and NiVF post-fusion (NiVF-PoF). Prior to virtual screening, the drug-likeness of Streptomyces spp. compounds was profiled using ADMET properties. From the 913 ADMET-filtered compounds, the subsequent targeted and confirmatory blind docking analysis revealed that S896 or virginiamycin M1, a known macrolide antibiotic, showed a maximum binding affinity with the NiVF proteins, suggesting a multi-targeting inhibitory property. In addition, the 200-ns molecular dynamics simulation and MM/PBSA analyses revealed stable and strong binding affinity between the NiVF-S896 complexes, indicating favorable interactions between S896 and the target proteins. These findings suggest the potential of virginiamycin M1, an antibiotic, as a promising multi-targeting antiviral drug. However, in vitro and in vivo experimental validations are necessary to assess their safety and efficacy.
(© 2024. The Author(s), under exclusive licence to Springer Nature Switzerland AG.)
Databáze: MEDLINE
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