To Explore the Potential Targets and Current Structure-based Design Strategies Utilizing Co-crystallized Ligand to Combat HCV

Curr Drug Targets. 2021;22(5):590-604. doi: 10.2174/1389450121999200727215020.

Abstract

Background: Hepatitis C Virus (HCV) belongs to the Hepacivirus family. HCV has been designated as a very dreadful virus as it can attack the liver, causing inflammation and even may lead to cancer in chronic conditions. It was estimated that 71 million people around the world have chronic HCV infection. World Health Organization (WHO) reported that about 399000 people died because of chronic cirrhosis and liver cancer globally. In spite of the abundance of availability of drugs for the treatment of HCV, however, the issue of drug resistance surpasses all the possibilities of therapeutic management of HCV. Therefore, to address this issue of 'drug-resistance', various HCV targets were explored to quest the evaluation of the mechanism of the disease progression.

Methods: An attempt has been made in the present study to explore the various targets of HCV involved in the mechanism(s) of the disease initiation and progression and to focus on the mode of binding of ligands, which are co-crystallized at the active cavity of different HCV targets.

Conclusion: The present study could predict some crucial features of these ligands, which possibly interacted with various amino acid residues responsible for their biological activity and molecular signaling pathway(s). Such binding mode may be considered as a template for the high throughput screening and designing of active congeneric ligands to combat HCV.

Keywords: Hepatitis C virus; co-crystallized ligand; drug resistance in HCV target; mode of binding; structure-based design; various potential HCV targets.

Publication types

  • Review

MeSH terms

  • Antiviral Agents* / pharmacology
  • Antiviral Agents* / therapeutic use
  • Hepacivirus / drug effects
  • Hepatitis C* / drug therapy
  • Humans
  • Ligands

Substances

  • Antiviral Agents
  • Ligands