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

초록

The HIV-1 infection epidemic remains a global healthproblem. Currentantiretroviral treatments are effective in controlling the progressionof a severe infection. However, the emergence of drug resistance requiresan urgent identification of new treatment regimes. HIV-1 reverse transcriptase(RTs) has been a successful therapeutic target owing to its high specificityand potent antiviral properties; therefore, it has become an essentialcomponent of current HIV-1 standard treatments. This study identifieda new HIV-1 RTs inhibitor (Compound #8) that is structurallyunique and greatly effective against HIV-1 through chemical libraryscreening and a medicinal chemistry program by analyzing the structure-activityrelationship (SAR). Further analysis of molecular docking and mechanismsof action demonstrated that Compound #8 is a novel typeof HIV-1 non-nucleoside reverse transcriptase inhibitor (NNRTI) witha flexible binding mode. Therefore, it exhibits great therapeuticpotential when combined with other existing HIV-1 drugs. Our currentstudies suggest that Compound #8 is a promising novelscaffold for the development of new HIV-1 treatments.

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