The Categories, Mechanisms and Features of Nonnucleoside Reverse Transcriptase Inhibitors of HIV-1

Abstract

AIDS, or acquired immune deficiency syndrome is a dangerous disease of our age, and is mainly caused by HIV-1. In the last decades, researchers have paid attention to the inhibitors of reverse transcriptase (RT) of HIV-1 as a promising candidate for antiviral drugs. The reverse transcriptase (RT) is a crucial enzyme in the life cycle of HIV-1, responsible for the conversion of viral RNA to proviral DNA which will be later integrated with the genome of infected cells. RT is composed of two function domains: an RNA and DNA-dependent polymerase domain and an RNase H domain, which are respectively responsible for the synthesis and hydrolysis of proviral DNA strands. A number of drugs targeting one of the domains or both have been designed, tested or approved for clinical use, among which the nonnucleoside reverse transcriptase inhibitors (NNRTIs) have gained their status for various advantages. Herein, the molecular mechanism of four kinds of main RT inhibitors-polymerase inhibitors, RNase H active site inhibitors, RNase H allosteric inhibitors and dual inhibitors are introduced, as well as the advantages, drawbacks and challenges of these drugs. Their mechanisms and challenges are discussed to promote a comprehensive understanding of the development of NRRTIs.