Identification of a Non-Nucleoside Reverse Transcriptase Inhibitor against Human Immunodeficiency Virus-1.

The HIV-1 infection epidemic remains a global health problem. Current antiretroviral treatments are effective in controlling the progression of a severe infection. However, the emergence of drug resistance requires an urgent identification of new treatment regimes. HIV-1 reverse transcriptase (RTs) has been a successful therapeutic target owing to its high specificity and potent antiviral properties; therefore, it has become an essential component of current HIV-1 standard treatments. This study identified a new HIV-1 RTs inhibitor (Compound #8) that is structurally unique and greatly effective against HIV-1 through chemical library screening and a medicinal chemistry program by analyzing the structure-activity relationship (SAR). Further analysis of molecular docking and mechanisms of action demonstrated that Compound #8 is a novel type of HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI) with a flexible binding mode. Therefore, it exhibits great therapeutic potential when combined with other existing HIV-1 drugs. Our current studies suggest that Compound #8 is a promising novel scaffold for the development of new HIV-1 treatments.