Computer-Aided Drug Repurposing of FDA-Approved Small Molecules Targeting NS5 RdRp for Zika Virus​

Jonelle Brown

Co-Presenters: Individual Presentation

College: The Dorothy and George Hennings College of Science, Mathematics and Technology

Major: Chemistry

Faculty Research Mentor: Supratik Kar

Abstract:

Zika virus (ZIKV) poses a global health threat due to its association with neurological complications and congenital malformations. With no FDA-approved treatments available, targeting the viral Non-structural 5 (NS5) RNA-dependent RNA polymerase (RdRp) presents a promising therapeutic strategy. This study employed an in silico drug repurposing approach using over 2,588 FDA-approved molecules from DrugBank, combined with virtual screening and QSAR modelling to predict inhibitory activity. Seven candidate compounds were identified, followed by ADMET profiling and molecular dynamics simulations, which led to the identification of three top leads (DB08818, DB11938, and DB01698) showing strong binding stability and therapeutic potential. Further refinement of binding free energies using MM-GBSA is underway to confirm their efficacy.

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Identifying Protein Targets of Novel Compounds with Broad-Spectrum Antifungal Activity