PhD defence Y. (Yunlong) Li

Drug Repurposing for Treating Hepatitis E Virus Infection
Promotor

Prof. dr. M.P. Peppelenbosch

Promotor

Prof. dr. R.A. de Man

Co-promotor

Dr. Q. Pan

Date
Tuesday 30 Aug 2022, 15:30 - 17:00
Type
PhD defence
Space
Professor Andries Querido room
Building
Education Center
Location
Erasmus MC
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On Tuesday, 30 August 2022, Y. Li will defend his PhD dissertation, entitled: 'Drug Repurposing for Treating Hepatitis E Virus Infection’.

Dissertation in short:

Hepatitis E remains a major public health challenge that provokes a tremendous burden of morbidity and mortality worldwide. Since the limited treatment options are available, 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. Thus, there is a clear need for developing drug repurposing of existing medication for treating HEV infection and understanding the potential mechanism-of-action of potent anti-HEV candidates. In this thesis, I propose to systematically screen in a safe-in-human broad-spectrum antiviral agents (BSAAs) library and repurpose the existing drugs that can be readily used in the clinic. I identified several potent inhibits HEV agents and focus on the leading candidates of HEV inhibitors. In Chapter 5, I 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, I 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, I 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, I 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.

More information

The public defence will begin exactly at 15.30 hrs. The doors will be closed once the public defence starts, latecomers can access the hall via the fourth floor. Due to the solemn nature of the ceremony, we recommend that you do not take children under the age of 6 to the first part of the ceremony.

A live stream link has been provided to the candidate.

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