The capsid protein of the Human Immunodeficiency Virus (HIV) is an attractive inhibition site. Its formation of the capsid core is crucial for viral infectivity. A compound, CAP-1, has been identified that binds to the N-terminal domain of the capsid protein (CAN) and inhibits capsid formation in vitro and in vivo, but the dissociation constant (Kd) is not within an acceptable range. We have been testing new compounds for potential inhibition with a Kd in the nanomolar range using NMR HSQC Titrations. The computer program, PyMOL, has been used to give a visual representation of the binding pocket conformation. A correlation has been found between the amount of unoccupied space within the pocket and the lower the Kd. A hybrid compound was formulated, which has adopted the best functional groups and features. The hybrid has given the best PyMOL results. Future work includes synthesis of the hybrid and NMR testing.

Creation of the hybrid compound for inhibition of HIV-1 capsid core formation using PyMOL

243rd National Meeting (2012)

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