Search for new therapeutics against HIV-1 via dual inhibition of RNase H and integrase: current status and future challenges.

Harsha Kharkwal, Banoth K Kumar, Sankaranarayanan Murugesan, Gautam Singhvi, Preeti Avasthi, Ankush Goyal, Joazaizulfazli Jamalis, Subhash Chander

Future medicinal chemistry 2021 Feb

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Reverse transcriptase and integrase are key enzymes that play a pivotal role in HIV-1 viral maturation and replication. Reverse transcriptase consists of two active sites: RNA-dependent DNA polymerase and RNase H. The catalytic domains of integrase and RNase H share striking similarity, comprising two aspartates and one glutamate residue, also known as the catalytic DDE triad, and a Mg2+ pair. The simultaneous inhibition of reverse transcriptase and integrase can be a rational drug discovery approach for combating the emerging drug resistance problem. In the present review, the dual inhibition of RNase H and integrase is systematically discussed, including rationality of design, journey of development, advancement and future perspective.

Citation

Harsha Kharkwal, Banoth K Kumar, Sankaranarayanan Murugesan, Gautam Singhvi, Preeti Avasthi, Ankush Goyal, Joazaizulfazli Jamalis, Subhash Chander. Search for new therapeutics against HIV-1 via dual inhibition of RNase H and integrase: current status and future challenges. Future medicinal chemistry. 2021 Feb;13(3):269-286