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

•Latest advances of HIV-1 integrase inhibitors focusing on molecular modeling.•Features and functionalities of these computational approaches.•Practices dealing with the ambiguities in drug discovery.•A general workflow of the discovery of novel inhibitors using virtual screening. 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. HIV-1 integrase is gaining popularity as a target for antiviral therapy of AIDS. A comprehensive review about the latest advances could provide a crucial underpinning for future developments of integrase inhibitors.