Thevetiaflavone As A Novel Dengue Serotype 3 Rna-Dependent Rna Polymerase Inhibitor: Insights From Molecular Docking And Pharmacokinetic Predictions

In the search for innovative antiviral solutions, this computational study highlighted thevetiaflavone as a potential inhibitor of DENV-3 RNA-dependent RNA polymerase (DENV-3 RdRp). Molecular docking studies demonstrate that thevetiaflavone possesses a binding affinity of –7.3 Kcal/mol, which is higher than that of the conventional antiviral drug Ribavirin, noted at –6.4 Kcal/mol. The stability of the protein–ligand complex is reinforced by significant interactions with the amino acid residues ASP 664, CYS 709, and MET 761. Additionally, the hydrogen bonds formed between ARG 729 and SER 710 play a key role in firmly holding the ligand within the N-pocket of the enzyme, which may interfere with the initiation of viral RNA synthesis. The stability of this protein–ligand complex was further supported by Molecular Flexibility Analysis using the CABSflex and iMODS platforms, both of which indicated a structurally stable interaction. Pharmacokinetic evaluation using SwissADME and ADMETlab 2.0 suggests that the compound possesses desirable drug-like properties, such as good oral bioavailability and low overall toxicity. However, the predicted risks of respiratory toxicity and possible mutagenicity have raised safety concerns. Thus, although thevetiaflavone has potential as a drug candidate, it is essential for future experimental validation to prioritize toxicological studies and efficacy assessments to confirm its safety as a therapeutic option for dengue fever.