Zinc C293 as a novel scaffold with dual activity against HIV-1 integrase and reverse transcriptase

HIV-1 drug resistance remains a major challenge in antiretroviral therapy, highlighting the need for new and more effective inhibitors. This study explores Zinc C293 as a potential dual inhibitor targeting two key HIV-1 enzymes: integrase (IN) and reverse transcriptase (RT). Initially identified through pharmacophore-based virtual screening, Zinc C293 was further analyzed using molecular docking and molecular dynamics (MD) simulations to understand its stability and interactions with IN. Further, we tested its ability to inhibit IN in in vitro assays. We also investigated its potential to inhibit RT through in silico studies, followed by in vitro validation. The results showed that Zinc C293 effectively blocked IN strand transfer (ST) activity and formed strong interactions with key RT residues, confirming its dual-inhibitory potential. Zinc C293 demonstrated significant activity against both targets when compared to the existing drugs. These findings suggest that Zinc C293 could be a promising candidate for next-generation antiretroviral therapies. Further studies are needed to fully explore its potential in overcoming drug resistance and improving HIV treatment outcomes.