Using cryo-EM for designing next-gen therapeutics against HIV

HIV currently infects almost 40 million people worldwide. The virus is responsible for ~2 million new infections per year and ~1 million deaths. Like all retroviruses, HIV integrates a viral DNA copy of its RNA genome into host chromatin, thereby establishing a permanent and irreversible infection in the target cell. Integration depends on the obligate formation of a large oligomeric nucleoprotein complex containing the viral integrase enzyme assembled on viral DNA ends, commonly referred to as an intasome. Intasomes are also targeted by the latest generation antiretrovirals, integrase strand transfer inhibitors (INSTIs). Cryo-EM methods are beginning to shed light on the structures of HIV intasomes and how INSTIs bind, revealing how small changes in the integrase active site can have significant implications for drug binding. This work has implications for expanding effective treatments available for HIV-infected individuals. In this webcast, Dr. Dmitry Lyumkis will describe how advances in cryo-EM are facilitating structure-based drug design targeting HIV integration.

Learning Objectives:

1. The basics of single-particle cryo-EM, including the latest technical advances that are facilitating high-resolution structural studies

2. The biology of HIV integration, and why this step of the viral lifecycle is vulnerable to inhibition

3. How single-particle cryo-EM is becoming applicable to drug design and helping to combat the global HIV epidemic