Recent advances on dual inhibitors targeting HIV reverse transcriptase associated polymerase and ribonuclease H

Reverse transcriptase (RT) plays an indispensable role in the replication of human immunodeficiency virus (HIV) through its associated polymerase and ribonuclease H (RNase H) activities during the viral RNA genome transformation into proviral DNA. Due to the fact that HIV is a highly mutagenic virus and easily resistant to single-target RT inhibitors, dual inhibitors targeting HIV RT associated polymerase and RNase H have been developed. These dual inhibitors have the advantages of increasing efficacy, reducing drug resistance, drug-drug interactions, and cytotoxicity, as well as improving patient compliance. In this review, we summarize recent advances in polymerase/RNase H dual inhibitors focusing on drug design strategies, and structure-activity relationships and share new insights into developing anti-HIV drugs.