Hepatitis E virus (HEV) infection can cause severe complications and high mortality in pregnant women, organ transplant recipients, patients with pre-existing liver disease and immunosuppressed patients. However, there are still unmet needs for treating HEV infections.
A recent study led by Dr. Wenshi Wang and Dr. Hongbo Guo (Xuzhou Medical University, Xuzhou, China) in collaboration with Dr. Qiuwei Pan and Prof. Luc J W van der Laan from Erasmus Medical Center screened a best-in-class drug repurposing library. The researchers identified vidofludimus calcium and pyrazofurin as novel anti-HEV entities. Vidofludimus calcium is the next-generation dihydroorotate dehydrogenase (DHODH) inhibitor in the phase 3 pipeline to treat autoimmune diseases or SARS-CoV-2 infection. Pyrazofurin selectively targets uridine monophosphate synthetase (UMPS).
The authors investigated the anti-HEV effects of both drugs in a range of cell culture models and human liver organoid models derived from different donors. Both drugs exhibited a sizeable therapeutic window against wild type as well as ribavirin treatment failure-associated HEV strains (Y1320H, G1634R). Mechanistically, their anti-HEV mode of action depends on the blockage of pyrimidine synthesis. Their combination with IFN-α resulted in synergistic antiviral activity.
Thus, vidofludimus calcium and pyrazofurin are potent anti-HEV drug candidates. Based on their antiviral potency, and also the favourable safety profile identified in clinical studies, these findings support the potential initiation of clinical studies to repurpose these drugs for treating chronic hepatitis E.
Read the full article (Virol Sin. 2023 Nov 18:S1995-820X(23)00138-4): DOI: 10.1016/j.virs.2023.11.006
