Advances in rationally designed dual inhibitors of HIV-1 reverse transcriptase and integrase.

Reverse transcriptase (RT) and integrase (IN) are two indispensable enzymes in human immunodeficiency virus type 1 (HIV-1) replication. RT is responsible for the transformation of the single-stranded RNA viral genome into double-stranded DNA, and IN catalyzes the integration of viral DNA into the host DNA. Although highly active antiretroviral therapy (HAART) combining nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs/NtRTIs) with nonnucleoside reverse transcriptase inhibitors (NNRTIs) or protease inhibitors (PIs) could suppress successfully HIV viral load and reduce evidently the mortality of HIV infected people, it involves the difficulty of perfect adherence, and other drawbacks such as viral rebound, toxicities and multi-drug resistances. Recently, rational drug design has become a dominant technique for the development of multi-target drugs. And the rationally designed dual inhibitors of HIV-1 RT and IN have become a hot topic of anti-HIV research. In this review, the advances in rationally designed dual inhibitors of HIV-1 RT and IN were summarized, including structurally diverse inhibitors, their structure-activity relationship (SAR) studies as well as binding mode analysis.