Small Molecular Inactivators of HIV

National Institute Of Diabetes And Digestive And Kidney Diseases

Investigators

Linked publications, trials & patents

Abstract

We have developed and studied our molecule both in the active form and as a prodrug. We have developed large-scale syntheses for these molecules and worked in collaboration to study their antiviral activity and evaluate their preclinical toxicity. Overall, the molecules show broad range of activity across a panel of HIV-1 clinical isolates in human PBMCs, demonstrate additive to synergistic antiviral interactions with other FDA-approved HIV drugs, and do not allow the generation of HIV resistant strains after 14 passages. There is no observable toxicity with our molecules. Our molecules have also been successfully developed into platforms for application as a microbicide. The lead molecule has also been shown to work in combination with an experimental vaccine to enhance protection from HIV infection. We are currently examining the detailed mechanism of these molecules, performing an in vivo study, closely examining the pharmacokinetics and metabolism, and exploring whether these molecules have activity against other diseases. We are now working on the second generation variants of the original molecule that will be suitable for use as an injectable formulation.