2026

What is the title of your project, and what is its primary focus?

The title of my project is “Structural, Biochemical, and Computational Approach to Decipher the Molecular Basis of HIV Negative Factor-Mediated Antagonism of Human SERINC5 for Antiviral Drug Discovery”. As one of the most important determinants of HIV pathogenicity, the function of HIV Negative Factor (Nef) is to degrade and remove several host integral membrane proteins that otherwise increase the resistance of cells to viral infection, one of which is the human SERINC5. The focus of the project is to determine the molecular and structural basis of the interaction between HIV Nef, SERINC5, and the human adaptor protein AP-2. Achieving this goal would help in identifying and designing small molecules that can block this critical interaction. 

How does your project align with the Center’s objectives?

The project aligns with the Center’s objectives—particularly the structural biology core—of understanding HIV virus-host complexes at the structural and mechanistic level. By utilizing state-of-the-art cryo-electron microscopes and data processing techniques, the details of the HIV-Nef, SERINC5, and AP-2 complex interactions will be elucidated. 

What is the most inspiring aspect of your research?

The goal of the research is to turn a detailed molecular understanding of HIV’s immune evasion into a tangible therapeutic strategy. At its core, the project reveals how HIV uses the Nef protein to disable a natural human defense (SERINC5) that would otherwise suppress viral infectivity. By resolving this interaction at near-atomic detail, it pinpoints how the virus can be substantially weakened. However, what I find most inspiring is the opportunity to integrate biochemistry with advanced computational methods to achieve the mentioned near-atomic detail. Beyond the immediate goals of this project, the approaches and expertise developed here will establish a powerful framework for tackling many other challenging problems in structural biology.

What are your thoughts on the importance of advancing our understanding of HIV–host protein complexes and expanding therapeutic targets and treatment strategies for HIV/AIDS?

Towards the goal of defeating HIV, advancing our understanding of HIV–host protein complexes are critical because many of HIV’s most important mechanism of actions come from its hijacking of host machinery. Interactions like the Nef–AP2–SERINC5 complex show that the virus actively dismantles cellular defenses to enhance infectivity. Expanding therapeutics targets and treatment strategies, for instance by targeting the host-virus interfaces, opens the possibility of more effective and robust therapies by preventing direct viral resistance mutations.