Susana Valente, an assistant professor at Scripps Florida,  is the principal investigator of the five-year NIH $3.4 million grant to study the mode of action and the therapeutic potential of a new compound that blocks a step of HIV replication not targeted by current therapies.

Susana Valente

Valente will lead research into the viral protein known as Tat, a potent activator of HIV gene expression, and a Tat inhibitor that is extremely effective at reducing viral output from acutely and chronically infected cells in culture. Most antiretroviral compounds only block new infections; a Tat inhibitor can reduce viral replication from cells already infected.

“Our main goal with this grant is to fully understand the underlying mechanism of this new compound’s inhibitory strength against Tat,” Valente said, “and then to evaluate its therapeutic potential in animal models. If that’s successful, the next obvious step would be to optimize it for use in human clinical trials.”

Despite recent advances, HIV/AIDS continues its deadly global march, affecting more than 35 million individuals worldwide. The virus stubbornly persists in infected subjects despite Highly Active Antiretroviral Therapy (HAART). This residual viremia is the major hurdle for HIV eradication. Valente’s newly identified Tat inhibitor defines a novel class of anti-viral drugs that could potentially inhibit viral production from stable reservoirs and reduce viral persistency during HAART.

“Initially, we though this compound was targeting another protein, but the data suggested that it was actually an inhibitor of Tat,” Valente said. “We soon discovered we had a powerful inhibitor of HIV-1 transcription in our hands—and that’s where we are today. This work was made possible by the great ongoing collaboration with Professor Phil Baran of Scripps California.”