Hepatitis C virus (HCV) proteases: structure, function and inhibition strategies

Area of Science:

• Virology
• Molecular Biology
• Hepatology

Background:

• Hepatitis C virus (HCV) is a major global health issue, causing chronic liver disease and cancer.
• Direct-acting antivirals (DAAs) have improved cure rates, but challenges like undiagnosed infections and limited access persist, particularly in low- and middle-income countries (LMICs).

Purpose of the Study:

• To explore the molecular biology of HCV, focusing on the NS2/3 and NS3/4A proteases.
• To understand how DAAs target these proteases and the mechanisms of drug resistance.
• To discuss future therapeutic strategies for HCV.

Main Methods:

• Review of the structure and function of NS2/3 and NS3/4A proteases in the HCV life cycle.
• Analysis of DAA mechanisms of action against these viral targets.
• Investigation of genetic mutations driving HCV drug resistance.

Main Results:

• The NS2/3 and NS3/4A proteases are essential for HCV polyprotein processing.
• NS3/4A protease is a validated target for DAAs, with several FDA-approved drugs available.
• HCV genetic diversity leads to drug-resistant strains, necessitating pan-genotypic DAAs.

Conclusions:

• Continued research into HCV protease function and resistance is vital for developing more effective and accessible treatments.
• Addressing challenges in LMICs is critical for global HCV eradication efforts.
• Exploring novel therapeutic approaches may overcome current treatment limitations.