Repurposing of DrugBank small molecules against Dengue virus capsid protein: an in silico study.

Abstract

Dengue virus (DENV) remains a pressing global health threat with no approved antiviral therapy to date. In this study, we explore the conserved hydrophobic pocket at the dimer interface of the dengue capsid protein as a novel target for antiviral intervention. Using a high-resolution capsid structure with modeled N-terminal disordered regions, we performed virtual screening of the entire DrugBank database employing AutoDock Vina to identify potential repurposable inhibitors. Six top-binding candidates were shortlisted based on docking scores and binding site specificity. These molecules were subjected to classical molecular dynamics (MD) simulations to evaluate complex stability, followed by thermal titration MD (TTMD) to assess interaction robustness under thermal stress. Three molecules-DB02152, DB08683, and DB13014-exhibited highly stable binding throughout both MD and TTMD analyses, with DB13014 (Hypericin) showing the highest thermal stability and favorable interaction energy. In silico ADMET profiling further validated the drug-like properties of these compounds, indicating acceptable oral bioavailability, low toxicity risk, and synthetic tractability. These findings highlight the dengue capsid hydrophobic pocket as a viable drug target and propose repurposing of small molecules as anti-dengue therapeutics.

Supplementary information: The online version contains supplementary material available at https://doi.org/10.1007/s40203-026-00738-w.