HIV-1 Gag is the master orchestrator of particle assembly. The central role of Gag at multiple
stages of the HIV lifecycle has led to efforts to develop drugs that directly target Gag and prevent
the formation and release of infectious particles. Until recently, however, only the catalytic site protease
inhibitors have been available to inhibit late stages of HIV replication. This review summarizes the
current state of development of antivirals that target Gag or disrupt late events in the retrovirus lifecycle
such as maturation of the viral capsid. Maturation inhibitors represent an exciting new series of antiviral
compounds, including those that specifically target CA-SP1 cleavage and the allosteric integrase
inhibitors that inhibit maturation by a completely different mechanism. Numerous small molecules
and peptides targeting CA have been studied in attempts to disrupt steps in assembly. Efforts to target CA have recently
gained considerable momentum from the development of small molecules that bind CA and alter capsid stability at
the post-entry stage of the lifecycle. Efforts to develop antivirals that inhibit incorporation of genomic RNA or to inhibit
late budding events remain in preliminary stages of development. Overall, the development of novel antivirals targeting
Gag and the late stages in HIV replication appears much closer to success than ever, with the new maturation inhibitors
leading the way.
Keywords: Gag, HIV, Antiretroviral, Virus assembly, Capsid, Matrix, Nucleocapsid, Allosteric integrase inhibitors, Bevirimat.
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