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.

HIV-1; NNRTI; novel chemical scaffold; phenotypic screening; reverse transcriptase; structure−activity relationship.