Development of HIV-1 integrase inhibitors: recent molecular modeling perspectives

Of the three viral enzymes essential to HIV replication, HIV-1 integrase (IN) is gaining popularity as a target for the antiviral therapy of AIDS. Substantial work focusing on IN has been done over the past three decades, which has facilitated and led to the approval of three drugs. Here, we discuss in detail the development of IN inhibitors between January 2012 and May 2014, with a particular focus on molecular simulation. We highlight controversial aspects of computational drug design and refer to alternative practices where appropriate. The analysis of these computational approaches provides some useful clues to the possible future discovery of novel IN inhibitors.