Repositioning antiviral phytoconstituents as broad-spectrum inhibitors of influenza A neuraminidase and human metapneumovirus fusion protein
- 1Laboratory of analytical and molecular chemistry, Faculty of Sciences Ben M’Sik, Hassan II University of Casablanca, Casablanca, Morocco
- 2Department of Chemistry, College of Science, United Arab Emirates University, Abu Dhabi, United Arab Emirates
Abstract
Viral respiratory infections still exist as a major global health concern. Influenza A viruses and human metapneumoviruses are among the main pathogens responsible for infections that can progress to severe acute respiratory forms. Despite the availability of certain therapeutic options, the need for effective treatment remains an issue. The exploration of innovative approaches based on medicinal plants, capable of simultaneously targeting several viruses, represents a promising strategic option for limiting the viral activity of these pathogens. In this work, an integrated computational workflow combining molecular docking, ADMET prediction, molecular dynamics (MD) simulations, and MM-PBSA binding free-energy analysis was applied to evaluate previously reported antiviral phytoconstituents for their broad-spectrum antiviral potential by simultaneously targeting influenza A virus neuraminidase (NA) (PDB ID: 2HT7) and the human metapneumovirus (HMPV) fusion protein (F) (PDB ID: 7SEJ). Molecular docking analyses identified 37 phytoconstituents with favorable multi-target binding affinities toward both NA and F proteins, exhibiting more favorable predicted binding energies than the reference compounds oseltamivir and ribavirin. In addition, ADMET prediction, including bioavailability assessment and analysis of pharmacokinetic and toxicological properties, identified several compounds with favorable profiles, notably compounds E10, M294, M329, C11, C5, and M274. MD simulations followed by MM-PBSA binding free-energy calculations further validated the stability and binding behavior of the highest-ranked protein–ligand complexes identified through the sequential screening workflow. Overall, compounds M294 and C11 emerged as the most promising broad-spectrum antiviral lead candidates against both influenza A NA and HMPV F protein. Nevertheless, these findings are based on computational predictions and require confirmation through in vitro antiviral assays followed by in vivo studies.
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BibTeX
@article{mounadi2026repositioning,
title = {{Repositioning antiviral phytoconstituents as broad-spectrum inhibitors of influenza A neuraminidase and human metapneumovirus fusion protein}},
author = {Nouh Mounadi and Hassan Nour and M’hammed El Kouali and Abdelouahid Samadi and Samir Chtita},
journal = {PLOS One},
year = {2026},
month = sep,
doi = {10.1371/journal.pone.0348517},
url = {https://doi.org/10.1371/journal.pone.0348517},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - Repositioning antiviral phytoconstituents as broad-spectrum inhibitors of influenza A neuraminidase and human metapneumovirus fusion protein
AU - Nouh Mounadi
AU - Hassan Nour
AU - M’hammed El Kouali
AU - Abdelouahid Samadi
AU - Samir Chtita
PY - 2026
DA - 2026/09/02
JO - PLOS One
DO - 10.1371/journal.pone.0348517
UR - https://doi.org/10.1371/journal.pone.0348517
AB - Viral respiratory infections still exist as a major global health concern. Influenza A viruses and human metapneumoviruses are among the main pathogens responsible for infections that can progress to severe acute respiratory forms. Despite the availability of certain therapeutic options, the need for effective treatment remains an issue. The exploration of innovative approaches based on medicinal plants, capable of simultaneously targeting several viruses, represents a promising strategic option for limiting the viral activity of these pathogens. In this work, an integrated computational workflow combining molecular docking, ADMET prediction, molecular dynamics (MD) simulations, and MM-PBSA binding free-energy analysis was applied to evaluate previously reported antiviral phytoconstituents for their broad-spectrum antiviral potential by simultaneously targeting influenza A virus neuraminidase (NA) (PDB ID: 2HT7) and the human metapneumovirus (HMPV) fusion protein (F) (PDB ID: 7SEJ). Molecular docking analyses identified 37 phytoconstituents with favorable multi-target binding affinities toward both NA and F proteins, exhibiting more favorable predicted binding energies than the reference compounds oseltamivir and ribavirin. In addition, ADMET prediction, including bioavailability assessment and analysis of pharmacokinetic and toxicological properties, identified several compounds with favorable profiles, notably compounds E10, M294, M329, C11, C5, and M274. MD simulations followed by MM-PBSA binding free-energy calculations further validated the stability and binding behavior of the highest-ranked protein–ligand complexes identified through the sequential screening workflow. Overall, compounds M294 and C11 emerged as the most promising broad-spectrum antiviral lead candidates against both influenza A NA and HMPV F protein. Nevertheless, these findings are based on computational predictions and require confirmation through in vitro antiviral assays followed by in vivo studies.
SN - 1932-6203
ER -