Key result
Camptothecin and Raucaffricine outperformed Favipiravir in docking against Human Norovirus RdRp, with Raucaffricine showing superior thermodynamic binding (ΔG_bind = –189.6 kcal/mol).
Why the study?
Human Norovirus is an emerging public health threat with no approved antivirals, creating a need to explore novel therapeutic leads from phytochemicals.
Do phytochemicals like Camptothecin and Raucaffricine inhibit HNV RdRp better than Favipiravir in computational models?
Do phytochemicals like Camptothecin and Raucaffricine inhibit HNV RdRp better than Favipiravir in computational models?
Computational modeling identifies Camptothecin and Raucaffricine as promising natural inhibitors of Human Norovirus RNA-dependent RNA polymerase.
These in silico hits are hypothesis-generating; leaves open whether phytocompounds can advance as norovirus antivirals.
• First-of-its-kind integration of traditional medicinal phytocompounds with advanced computational methods to target Human Norovirus (HNV). • Discovery of three potent natural RdRp inhibitors (Raucaffricine, Camptothecin, Strictosidine) outperforming Favipiravir. • Dual profiling of binding strength and kinetics using MM-GBSA and metadynamics—highlighting Camptothecin’s longer residence time. • Network pharmacology analysis identifies TRIM29 as a key immune regulator in HNV pathogenesis. • Bridges the gap between CAM medicine with modern drug discovery , promoting evidence-based use of traditional systems in antiviral therapy. Human Norovirus (HNV) is an emerging public health threat with no approved antivirals. There is a need to explore novel therapeutic leads, particularly from phytochemicals with CAM and other branches of medicine. This study aimed to identify potential phytochemical inhibitors of the HNV RNA-dependent RNA polymerase (RdRp), a key enzyme in viral replication. This study aimed to identify potential phytochemical inhibitors of the HNV RNA-dependent RNA polymerase (RdRp), a key enzyme in viral replication. Fifty-one phytochemicals, selected from literature based on reported antiviral or ethnomedicinal evidences, were retrieved from PubChem and docked against the RdRp protein (PDB ID: 4LQ3) using AutoDock Vina. Drug-likeness was assessed via Swiss ADME. Subsequently, all-atom molecular dynamics simulations (500 ns) were conducted to investigate the stability of the ligand–protein complexes. Binding free energy was quantified using MM-GBSA, and dissociation kinetics were explored through metadynamics simulations. Strictosamide, Camptothecin, and Raucaffricine outperformed both the co-crystallized ligand and Favipiravir in docking. ADME analysis showed that Camptothecin and Raucaffricine possessed favourable drug-likeness and high gastrointestinal absorption, with no Lipinski’s or Veber’s violations. Dynamics simulations revealed that Camptothecin provided strong conformational stabilization of RdRp, whereas Raucaffricine displayed greater flexibility. MM-GBSA highlighted Raucaffricine’s superior thermodynamic binding (ΔG_bind = –189.6 kcal/mol), while metadynamics showed Camptothecin’s higher dissociation energy barrier (ΔG_off = 14.5 kcal/mol), indicating longer target residence time. This integrative computational study identifies Camptothecin and Raucaffricine as promising anti-viral candidates to be considered against HNV. While Raucaffricine demonstrated stronger thermodynamic affinity, Camptothecin exhibited superior kinetic stability, which may enhance pharmacological efficacy.
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Fakola et al. (2025) studied Human Norovirus (HNV). Camptothecin and Raucaffricine vs. Favipiravir and co-crystallized ligand was evaluated on Binding free energy and dissociation kinetics against HNV RdRp. Camptothecin and Raucaffricine outperformed Favipiravir in docking against Human Norovirus RdRp, with Raucaffricine showing superior thermodynamic binding (ΔG_bind = –189.6 kcal/mol).
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