PhD awarded to Yunlong Li on hepatitis E research

On 30 August, Yunlong Li defended his PhD thesis on the development of antiviral therapy for treating hepatitis E virus (HEV) infection at Erasmus University Rotterdam, the Netherlands.

In 2017, Yunlong Li started his PhD research in the group of Dr. Qiuwei Abdullah Pan, at Erasmus University Medical Center Rotterdam. Since limited treatment options are available for treating hepatitis E patients, there is a clinical need for further development of new antiviral therapies against HEV infection. Drug repurposing has emerged as an attractive strategy to discover new applications for existing drugs. In this thesis, Yunlong systematically screen in a safe-in-human broad-spectrum antiviral agents library to repurpose the existing drugs that hopefully can be readily used in the clinic. He identified several agents with anti-HEV activity but focused on the leading candidates of HEV inhibitors. In Chapter 5, Yunlong identified gemcitabine, a widely used anti-cancer drug, potently inhibits HEV infection. Unexpectedly, it functions through the activation of interferon-like response via STAT1 phosphorylation but is independent of Janus kinases. In Chapter 6, he found ivermectin, an FDA-approved anti-parasitic drug, effectively inhibits HEV infection and the mechanism-of-action of ivermectin is associated with the host nuclear transport protein importin α1. In Chapter 7, he showed that macrolide antibiotic azithromycin is a potent HEV inhibitor, and the anti-HEV activity of azithromycin is independent of its induction of interferon-like response. In Chapter 8, Yunlong studied niclosamide, a widely used anthelmintic drug, as a potent inhibitor of HEV replication by inhibiting NFκB signaling but independent of STAT3. These findings provide new strategies to develop new antiviral therapies for combating HEV infection.

The full thesis can be openly accessed:

Drug Repurposing for Treating Hepatitis E Virus Infection