In Silico Identification of Endemic Plant-Derived Phytocompounds Targeting H5N1 Influenza Proteins via Molecular Docking and ADME Profiling.

Introduction: This study investigates the molecular docking of 306 phytochemicals from Iris, Daphne, and Chrysosplenium species against three key proteins of the H5N1 influenza virus: neuraminidase, polymerase, and hemagglutinin. Phytochemicals are recognized for their antiviral potential, but interactions between compounds from these genera and H5N1 proteins remain underexplored. Given the ongoing threat of H5N1, identifying novel inhibitors is essential. The main intent is to evaluate the binding affinities of selected phytochemicals through molecular docking and assess the drug-likeness of top candidates using pharmacokinetic and physicochemical filters.

Methods: Molecular docking was performed for 306 phytochemicals against the three H5N1 proteins. Fourteen promising compounds were further screened for physicochemical properties, compliance with Lipinski's Rule of Five, Veber's Rule, and PAINS alerts.

Results: All compounds exhibited no PAINS alerts, with several conforming to Lipinski's Rule of Five and Veber's Rule. Edgeworoside A emerged as the top-performing compound, showing strong binding affinity across all three targets and favorable interaction profiles. Triumbellin and daphnogi-rin A exhibited significant binding affinity for hemagglutinin and neuraminidase, as well as for polymerase, respectively. Compounds such as 3-isobutenylquercetin, irisoid E, junipegenin A, daphne-toxin, and excoecariatoxin exhibited high binding potential without violating drug-likeness criteria.

Conclusion: Several phytochemicals, particularly edgeworoside A, demonstrate promising multi-target potential against H5N1 influenza proteins. These findings highlight the therapeutic relevance of compounds from underexplored plant genera and support their further development through in vitro, in vivo, and preclinical studies.