Peptide inhibition of HIV-1: current status and future potential

More than 2 decades of intensive research has focused on defining replication mechanisms of HIV type 1 (HIV-1), the etiologic agent of AIDS. The delineation of strategies for combating this viral infection has yielded many innovative approaches toward this end. HIV-1 is a lentivirus in the family retroviridae that is relatively small with regard to both structure and genome size, having a diploid RNA genome of approximately 9 kb, with only three major genes and several gene products resulting from alternate splicing and translational frameshifting. Most marketed drugs for treating AIDS are inhibitors of HIV-1 reverse transcriptase or protease enzymes, but new targets include the integrase enzyme, cell surface interactions that facilitate viral entry, and also virus particle maturation and assembly. The emergence of drug-resistant variants of HIV-1 has been the main impediment to successful treatment of AIDS. Thus, there is a pressing need to develop novel treatment strategies targeting multiple stages of the virus life-cycle. Research efforts aimed at developing successful means for combating HIV-1 infection have included development of peptide inhibitors of HIV-1. This article summarizes past and current endeavors in the development of peptides that inhibit replication of HIV-1 and the role of peptide inhibitors in the search for new anti-HIV drugs.