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.