Flavonoids from Pterogyne nitens Inhibit Hepatitis C Virus Entry

Area of Science:

• Virology
• Natural Product Chemistry
• Hepatology

Background:

• Hepatitis C virus (HCV) infection is a major global health concern, leading to significant liver disease and transplantation needs.
• Current HCV therapies, including interferon-α, ribavirin, and direct-acting antivirals (DAAs), face challenges such as high cost, severe side effects, and emerging drug resistance.
• There is a critical need for novel, efficient, and potentially safer anti-HCV agents.

Purpose of the Study:

• To investigate the antiviral effects of sorbifolin (1) and pedalitin (2), two flavonoids isolated from Pterogyne nitens, against Hepatitis C virus (HCV) replication.
• To evaluate the potential of these flavonoids as novel therapeutic candidates for HCV infection.

Main Methods:

• Sorbifolin (1) and pedalitin (2) were tested for anti-HCV activity using genotype 2a JFH-1 subgenomic replicons and infectious virus systems.
• In vitro assays were conducted at non-cytotoxic concentrations to assess inhibition of viral entry, replication, and release.
• Mechanistic studies were performed to elucidate the mode of action for the observed antiviral effects.

Main Results:

• Both flavonoids demonstrated significant inhibition of HCV entry at non-cytotoxic concentrations, with pedalitin (2) showing 78.7% inhibition and sorbifolin (1) showing 45.0% inhibition.
• Pedalitin (2) inhibited HCV entry through a dual mechanism involving direct action on virus particles and interference with host cell factors.
• Sorbifolin (1)'s anti-HCV activity was primarily attributed to a virucidal effect on the virus particles.
• Neither flavonoid exhibited inhibitory effects on HCV replication or viral release from infected cells.

Conclusions:

• Sorbifolin (1) and pedalitin (2) possess in vitro anti-HCV activity, specifically by inhibiting viral entry.
• These findings represent the first report of anti-HCV activity for these two flavonoids.
• The distinct mechanisms of action suggest potential for developing new therapeutic strategies against HCV.