HIV-1 reverse transcriptase (RT) is responsible for reverse transcription of viral single-stranded RNA to double-stranded DNA, which plays an important role in the replication cycle of HIV-1 and has been identified as a key target for anti-HIV-1 drug discovery. Among HIV-1 RT inhibitors, allosteric inhibitors acting on non-catalytic sites have the advantages of high efficiency and low cytotoxicity, which are the focus of the research on anti-HIV-1 inhibitors. Great progress has been achieved in the structural biology of HIV-1 RT, which significantly facilitated the development of RT allosteric inhibitors. Herein, we provided a detailed review of the co-crystal structures of small molecule allosteric inhibitors in complex with RT reported in the last decade. Moreover, the strategies to discover novel and efficient inhibitors based on co-crystal structures have also been discussed, expecting to provide a reference for the development of the next-generation anti-HIV-1 drugs.

HIV-1  /  Reverse transcriptase  /  Anti-HIV-1 drugs  /  NNRTIs  /  Structural biology  /  Allosteric inhibitors  /  Drug design  /  Drug resistance