Inactivation of HIV-1 by Metalloporphyrin Compounds

Lillian Seu, University of California, San Francisco
Advisor: Joseph McCune
Basic Biomedical Sciences
Dissertation Award

In the past decade, antiretroviral HIV-1 medication has transformed the course of the HIV-1 epidemic in both developed and developing countries alike. However, as more HIV-1 infected patients receive the medication in the population, the problems of high resistance escape mutation rates as well as the complications of personal long-term antiretroviral use warrant a greater effort to identify alternative drug candidates to prevent the transmission of HIV-1.

This research proposal outlines the ways in which metalloporphyrins, a novel class of drug compounds, can be a potential drug candidate to inhibit the infection, replication and propagation of HIV-1 virus. Heme is one type of metalloporphyrin that is metabolized naturally in host mammalian organisms, and is the chemical for a myriad of proteins. It is an important house-keeping molecule that is tightly regulated in the course of red blood cell turnover. In the past, researchers have studied the effects of how metalloporphyrin compounds such as heme can inhibit HIV-1 replication in tissue cultures when administered in high concentrations. However, the exact method of how these metalloporphyrin compounds can inactivate HIV-1 is not clear. In order to utilize metalloporphyrins as a novel therapeutic, it is essential that the exact ways in which various HIV-1 genes are inhibited are known. This research proposal hopes to address this mechanism by studying the interaction of metalloporphyrins with three candidate HIV-1 genes that are responsible for the fusion, propagation, and the replication of the virus.

Due to issues such as escape mutations and long-term side effects of existing anti-retroviral medications, it becomes important and necessary to explore alternative drug candidates- particularly ones with a favorable bioavailability and metabolic profiles such as metalloporphyrins. The studies outlined in this proposal will elucidate whether metalloporphyrin compounds could represent a new class of antiretroviral drugs in the treatment of chronic HIV-1 infection.