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

Published: 21 November 2024 Publication History

Abstract

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.

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Highlights

The antiviral potential of Streptomyces spp. metabolites against the Nipah virus matrix protein was investigated using CADD methods.
Six metabolites exhibited inhibitory potential against the main substrate-binding site of the Nipah virus matrix protein.
Five metabolites exhibited inhibitory potential against the dimerization site of the Nipah virus matrix protein.
Nargenicin A1 requires further structural modification to enhance its binding affinity and inhibit both target regions.

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    Information & Contributors

    Information

    Published In

    cover image Computational Biology and Chemistry
    Computational Biology and Chemistry  Volume 112, Issue C
    Oct 2024
    820 pages

    Publisher

    Elsevier Science Publishers B. V.

    Netherlands

    Publication History

    Published: 21 November 2024

    Author Tags

    1. AD4
    2. ADMET
    3. CID
    4. GROMACS
    5. MD
    6. MMPBSA
    7. MMGBSA
    8. NiV
    9. NiV-M
    10. NVT
    11. NPT
    12. PCA
    13. PBC
    14. RMSD
    15. RMSF
    16. Ro5
    17. TPSA

    Author Tags

    1. Nipah virus
    2. Streptomyces
    3. docking
    4. ADMET
    5. Molecular dynamics
    6. Virtual screening
    7. In silico

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