Hepatitis C virus and natural compounds: a new antiviral approach?

Abstract

Hepatitis C is a major global health burden with an estimated 160 million infected individuals worldwide. This long-term disease evolves slowly, often leading to chronicity and potentially to liver failure. There is no anti-HCV vaccine, and, until recently, the only treatment available, based on pegylated interferon and ribavirin, was partially effective, and had considerable side effects. With recent advances in the understanding of the HCV life cycle, the development of promising direct acting antivirals (DAAs) has been achieved. Their use in combination with the current treatment has led to encouraging results for HCV genotype 1 patients. However, this therapy is quite expensive and will probably not be accessible for all patients worldwide. For this reason, constant efforts are being made to identify new antiviral molecules. Recent reports about natural compounds highlight their antiviral activity against HCV. Here, we aim to review the natural molecules that interfere with the HCV life cycle and discuss their potential use in HCV therapy.

Figure 1

Hepatitis C virus (HCV) life cycle and targets of the most potent natural inhibitors. First, HCV binds to non-specific factors glycosaminoglycans (GAG) and LDL receptor (LDL-R) present at the cell surface (attachment step). Then, the viral particle is directed to specific entry factors (entry step), the scavenger receptor class B type I (SR-BI), the tetraspanin CD81 and the tight junction proteins claudin-1 (CLDN1) and occludin (OCLN). The virus is internalized by endocytosis and the viral genome is released into the cytosol of the cell after fusion with endosomes (fusion step). Next, the translation and the polyprotein processing take place and RNA is replicated (replication step). In the late stages of the cycle, the virion is assembled (assembly step) in the vicinity of cytoplasmic lipid droplets (LD) and is released from the cell. Finally, the released virions can infect adjacent cells by cell-free transmission or cell-to-cell transmission. The affected steps of the viral cycle are in black. The natural compounds are in red. EGCG: epigallocatechin-3-gallate; ER: endoplamic reticulum.