HIV/AIDS continues to be a global health problem responsible for millions of deaths each year. Despite approval and clinical use of a variety of anti-HIV therapeutics, the emergence of HIV strains resistant to existing therapies and side effects of drug regimens make new target identification and lead discovery a continuing priority.  Entry inhibitors are an emerging class of therapeutics that interfere with attachment, fusion, or entry of HIV-1 into cells. HIV entry occurs through recognition of HIV's viral envelope glycoprotein gp120 with target cell receptors CD4 followed by interactions with GPCR coreceptors CCR5 or CXCR4. We describe studies that allowed us to identify synthetic peptides derived from the second extra cellular loop of CCR5 that have the ability to inhibit viral entry by CCR5- as well as CXCR4-using HIV strains. Using NMR we prove that these peptides bind gp120 directly and thus can be used as templates to design a new group of HIV entry inhibitors.

Synthetic CCR5-derived peptides that inhibit HIV entry

243rd National Meeting (2012)

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