Performance of sofosbuvir and NITD008 in extrahepatic neuronal cells against HEV

IF 4.5 2区 医学 Q1 PHARMACOLOGY & PHARMACY Antiviral research Pub Date : 2024-05-31 DOI:10.1016/j.antiviral.2024.105922
Michelle Jagst , André Gömer , Daniel Todt , Eike Steinmann
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Abstract

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.

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索非布韦和 NITD008 在肝外神经元细胞中抗击 HEV 的效果。
戊型肝炎是一种被低估的疾病,估计每年导致 2 千万人感染,多达 7 万人死亡。感染者大多无症状,但孕妇的死亡率可高达 25%,免疫力低下的患者则会转为慢性感染。戊型肝炎病毒(HEV)感染与一系列肝外表现有关,包括一系列神经系统症状。目前的治疗方法仅限于利巴韦林等非特异性抗病毒药物,但最近出现了索非布韦和 NITD008 等重新设计用途的病毒聚合酶抑制剂来抑制戊型肝炎病毒的复制。在这里,我们评估了这些药物在各种神经元衍生细胞系中的疗效,以确定它们在肝脏外的效力。我们的研究结果表明,与肝细胞相比,这两种药物(尤其是索非布韦)在神经元细胞中的疗效都有所下降。在开发针对 HEV 的直接作用抗病毒药物及其在肝外复制位点的效力时应考虑到这些结果。
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来源期刊
Antiviral research
Antiviral research 医学-病毒学
CiteScore
17.10
自引率
3.90%
发文量
157
审稿时长
34 days
期刊介绍: Antiviral Research is a journal that focuses on various aspects of controlling viral infections in both humans and animals. It is a platform for publishing research reports, short communications, review articles, and commentaries. The journal covers a wide range of topics including antiviral drugs, antibodies, and host-response modifiers. These topics encompass their synthesis, in vitro and in vivo testing, as well as mechanisms of action. Additionally, the journal also publishes studies on the development of new or improved vaccines against viral infections in humans. It delves into assessing the safety of drugs and vaccines, tracking the evolution of drug or vaccine-resistant viruses, and developing effective countermeasures. Another area of interest includes the identification and validation of new drug targets. The journal further explores laboratory animal models of viral diseases, investigates the pathogenesis of viral diseases, and examines the mechanisms by which viruses avoid host immune responses.
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