PT  - JOURNAL ARTICLE
AU  - Kwok-Fong Chan
AU  - Ser-Xian Phua
AU  - Chinh Tran-To Su
AU  - Samuel Ken-En Gan
TI  - Inhibiting HIV-1 and MMLV Reverse Transcriptase: The potential of an Allosteric Broad-Spectrum Inhibitor
AID  - 10.1101/699470
DP  - 2019 Jan 01
TA  - bioRxiv
PG  - 699470
4099  - http://biorxiv.org/content/early/2019/07/13/699470.short
4100  - http://biorxiv.org/content/early/2019/07/13/699470.full
AB  - Since drug resistance mutations in HIV-1 have been increasingly reported to resist most of the current drug repertoire in the antiretroviral therapy, there is a demand for new drugs. In this study, we focused on the viral enzyme Reverse Transcriptase (RT) as it is a good drug target given its absence in non-viruses. Through a reverse transcription assay screen, we found two out of forty compounds from the NCI Diversity Set V to inhibit HIV-1 RT activity. The less potent compound also inhibited MMLV RT. Molecular docking, structural conservation and binding pocket analyses suggested similar binding mechanisms of the dual inhibitor to the targets, implying that the phenylbenzoic scaffold may be potentially used to design broad-spectrum inhibitors against multiple Reverse Transcriptase enzymes from multiple viruses.