Peter Mercredi, Ph.D.


Chemistry and Biochemistry 2014

Area of Doctoral Study: Biochemistry
Undergraduate Institute: City College of New York

Research Advisor:  Michael F. Summers, Ph.D.

Current Position: Postdoctoral Fellow, St. Jude’s Research Hospital

Description of Research

The Human Immunodeficiency virus type 1 (HIV-1), the causative agent of AIDS, remains a global epidemic. According to UNAIDS, in 2010 over 34 million people worldwide were living with HIV/AIDS. A vaccine remains elusive; however there has been great strides in reducing viral loads through the development of highly active antiretroviral (HAART) therapy, which largely targets two of the proteins (protease and reverse transcriptase) encoded by the virus. Secondary to patient noncompliance, drug resistant strains have begun to emerge, making the discovery of antiretroviral agents that target other viral components necessary. An area that has shown promise is the development of inhibitors that target viral assembly. Successes of antiassembly drugs, in hepatitis B virus (HBV) and picornaviruses, suppress infectivity by inhibiting disassembly of capsid shells. Recent work to apply this approach on HIV-1 capsid (CA) resulted in identification of a small molecule CAP-1 that binds to CA inhibiting proper maturation of CA cores and reducing viral infection, in vivo. This proof of principle provides promise in the development of agents to target other structural proteins implicated in assembly. One of these targets is the matrix (MA) domain of Gag, essential in the late phase for membrane targeting and Envelope protein recruitment. Development of such inhibitors requires in-depth characterization of MA roles during retroviral assembly. My focus is on the myristylated matrix. Studies have observed that subtle mutations in HIV-1 MA can retarget Gag assembly to intracellular compartments. Structurally characterizing how these mutations result in atypical membrane targeting that may elucidate key features in MA for the development of novel HIV inhibitors.