Strategies to Preclude Hepatitis C Virus Entry

Abstract

Without a preventive vaccine, hepatitis C virus (HCV) remains an important pathogen worldwide with millions of carriers at risk of end-stage liver diseases. Despite the introduction of novel direct-acting antivirals (DAAs), resistance problems, challenges with the difficult-to-treat populations and high costs limit the widespread application of these drugs. Antivirals with alternative mechanism(s) of action, such as by restricting viral entry or cell-to-cell spread, could help expand the scope of antiviral strategies for the management of hepatitis C. Transfusion-associated HCV infection remains another issue in endemic and resource-limited areas around the world. This chapter describes some of the latest developments in antiviral strategies to preclude HCV entry, such as through monoclonal antibodies and small molecules, as well as measures to enhance the safety of therapeutic plasma products in blood transfusion.

Methanolic Extract of Rhizoma Coptidis Inhibits the Early Viral Entry Steps of Hepatitis C Virus Infection

“…The polyprotein upon translation is processed by viral and host proteases to yield 10 matured protein including structural proteins, Core, E1, E2, and p7 ion channel, as well as non-structural proteins NS2, NS3, NS4A, NS4B, NS5A, and NS5B [1]. HCV entry into the host hepatocytes is mediated by interaction with several notable cell surface and tight junction receptors/co-receptors including heparin sulfate proteoglycans (HSPG), cluster of differentiation 81 (CD81), low density lipoprotein receptor (LDLR), scavenger receptor class B type I (SR-BI), claudin-1 (CLDN1), and occludin (OCLN) [2,3]. Additional factors that can influence viral entry include apolipoprotein E (ApoE), which is incorporated on infectious HCV virions [4], and can function as an exchangeable apolipoprotein between secreted ApoE-associated lipoproteins and the HCV lipoviroparticle (LVP) to enhanced HCV infection [5].…”