Performance of sofosbuvir and NITD008 in extrahepatic neuronal cells against HEV

• Published in: Antiviral research 2024-07, Vol.227, p.105922, Article 105922
• Main Authors: Jagst, Michelle, Gömer, André, Todt, Daniel, Steinmann, Eike
• Format: Article
• Language: English
• Subjects: Antivirals; Hepatitis E virus; Neuronal cells; NITD008; Sofosbuvir
• ISSN: 0166-3542; 1872-9096; 1872-9096
• DOI: 10.1016/j.antiviral.2024.105922

Hepatitis E is an underestimated disease, leading to estimated 20 million infections and up to 70,000 deaths annually. Infections are mostly asymptomatic, but can reach mortality rates up to 25% in pregnant women or become chronic in immunocompromised patients. Hepatitis E virus (HEV) infection have been associated with a range of extrahepatic manifestations, including a spectrum of neurological symptoms. Current therapy options are limited to non-specific antivirals like ribavirin, but recently, repurposed viral polymerase inhibitors like sofosbuvir and NITD008 were described to inhibit HEV replication. Here, we evaluated the efficacy of these drugs in various neuronal-derived cell lines to determine their potency outside the liver. Our findings indicate that both drugs, especially sofosbuvir, exhibited reduced efficacy in neuronal cells compared to hepatic cells. These results should be taken into account in the development of direct-acting antivirals for HEV and their potency at extrahepatic replication sites. •The polymerase inhibitor sofosbuvir and NITD008 are potential drug candidates for the treatment of HEV infections.•Both drugs induce a decrease in HEV infection and replication in neuronal-derived cells.•Sofosbuvir and NITD008 exhibited diminished efficacy in neuronal-derived cells compared to hepatoma cells.