Host-targeting antivirals for chronic viral infections of the liver.

IF 4.5 2区医学 Q1 PHARMACOLOGY & PHARMACY

Antiviral research Pub Date : 2025-02-01 Epub Date: 2024-12-21 DOI:10.1016/j.antiviral.2024.106062

Nicola Frericks, Mara Klöhn, Frauke Lange, Lilli Pottkämper, Arnaud Carpentier, Eike Steinmann

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Abstract

Infection with one or several of the five known hepatitis viruses is a leading cause of liver disease and poses a high risk of developing hepatocellular carcinoma upon chronic infection. Chronicity is primarily caused by hepatitis B virus (HBV) and hepatitis C virus (HCV) and poses a significant health burden worldwide. Co-infection of chronic HBV infected patients with hepatitis D virus (HDV) is less common but is marked as the most severe form of chronic viral hepatitis. Hepatitis A virus (HAV) and hepatitis E virus (HEV) primarily cause self-limiting acute hepatitis. However, studies have also reported chronic progression of HEV disease in immunocompromised patients. While considerable progress has been made in the treatment of HCV and HBV through the development of direct-acting antivirals (DAAs), challenges including drug resistance, incomplete viral suppression resulting in failure to achieve clearance and the lack of effective treatment options for HDV and HEV remain. Host-targeting antivirals (HTAs) have emerged as a promising alternative approach to DAAs and aim to disrupt virus-host interactions by modulating host cell pathways that are hijacked during the viral replication cycle. The aim of this review is to provide a comprehensive overview about the major milestones in research and development of HTAs for chronic HBV/HDV and HCV infections. It also summarizes the current state of knowledge on promising host-targeting therapeutic options against HEV infection.

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肝脏慢性病毒感染的宿主靶向抗病毒药物

感染五种已知肝炎病毒中的一种或几种是肝脏疾病的主要原因，慢性感染后发展为肝细胞癌的风险很高。慢性主要由乙型肝炎病毒（HBV）和丙型肝炎病毒（HCV）引起，在世界范围内造成重大健康负担。慢性乙型肝炎病毒感染患者同时感染丁型肝炎病毒（HDV）的情况较少见，但被认为是最严重的慢性病毒性肝炎。甲型肝炎病毒（HAV）和戊型肝炎病毒（HEV）主要引起自限性急性肝炎。然而，研究也报道了免疫功能低下患者的HEV疾病慢性进展。虽然通过开发直接作用抗病毒药物（DAAs），在治疗HCV和HBV方面取得了相当大的进展，但挑战仍然存在，包括耐药性、病毒抑制不完全导致无法实现清除以及缺乏针对HDV和HEV的有效治疗方案。宿主靶向抗病毒药物（hta）已成为DAAs的一种有希望的替代方法，旨在通过调节病毒复制周期中被劫持的宿主细胞途径来破坏病毒与宿主的相互作用。本综述的目的是全面概述慢性HBV/HDV和HCV感染的hta研究和开发的主要里程碑。它还总结了目前针对HEV感染的有希望的宿主靶向治疗方案的知识状况。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

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.