Drug Repurposing for Rabies Treatment: A Computational Analysis of 14 Agents

This study explores the repurposing potential of 14 drugs (Emtricitabine, Famciclovir, Acyclovir, Stavudine, Cidofovir, Tinidazole, Ribavirin, Valaciclovir, Nevirapine, Atazanavir, Rilpivirine, Dasabuvir, Raltegravir, Elvitegravir) against the rabies virus glycoprotein pre-fusion trimer complexed with neutralizing antibody RVA122. Using docking and NAMD simulations, a drug ranking system considers key properties (docking score, hepatotoxicity, micro nuclear testing, human intestinal absorption, bioavailability, and blood-brain barrier (BBB) permeability). Excluding drugs with negative BBB (Atazanavir, Rilpivirine, Raltegravir, Elvitegravir), the top five candidates are Emtricitabine, Famciclovir, Acyclovir, Stavudine, and Cidofovir, showing promise for rabies treatment. In vitro and in vivo analyses are imperative for comprehensive validation, including drugs with negative BBB, as alternative mechanisms may contribute to therapeutic efficacy. This approach offers a cost-effective strategy for potential rabies treatment.