Asst. Prof. Xiao, Tianshu

Virus envelope protein is responsible for interacting with host receptors and mediating membrane fusion and entry, which is historically a focus in antiviral therapy development. My research focuses on antiviral inhibitor development based on insights gained from structure of viral fusion protein, eg. flavivirus E protein and coronavirus S protein. Leveraging on different drug discovery strategies, we are developing small molecule and peptide-based inhibitors to block the membrane fusion process mediated by these proteins. For example, we develop inhibitors capturing a traditionally challenging target on flavivirus E protein through an in-house developed antibody-guided platform and structure-based design. Another example is the AI-based peptidic inhibitor design targeting S protein of coronavirus, which has been rarely explored as a drug target because many conserved regions on S are not suitable for wet lab-based drug discovery. Here, we utilize AI-based approaches to design inhibitors capturing hotspots and hidden pockets on the S protein. With a combination of structural and biophysical approaches, we aim to find out broad-spectrum antiviral drug candidates with clear mechanisms and in vitro/ in vivo characterization.

Research Areas

Virus, structural biology, drug development, AI-based de novo design, membrane fusion