One million Americans are living with HIV/AIDS and 50,000 Americans  per year are newly infected with the disease. The evolution of multi- drug resistant HIV makes the virus difficult to target without combination therapy, and there is a need for new inhibitors of HIV-1  replication.  Using a combination of computer-aided drug discovery protocols and in vitro testing, the Cocklin lab has identified new small molecules that inhibit the HIV-1 capsid protein, targeting a particular pocket that is the binding site for host cell proteins.  The compounds have nanomolar antiviral potency and affinity for the HIV-1 capsid protein and reasonable metabolic stability as assessed by microsomal stability assays.  Further compound optimization is underway to improve the ADME/PK properties and to investigate enantioselectivity compared to the racemates.