Washington, Feb 19 — Hepatitis C virus (HCV) infection affects about 4.1 million people in the United States alone and is the primary cause of liver cirrhosis and liver cancer. Current therapy against the infection is not particularly effective.
Daclatasvir, a direct acting antiviral (DAA) agent, targets one of the HCV proteins NS5A and causes the fastest viral decline, within 12 hours of treatment ever seen with anti-HCV drugs.
An interdisciplinary effort by mathematical modellers, clinicians and molecular virologists has revealed that daclatasvir has two main modes of action against HCV and also yields a new, more accurate estimate of the HCV half-life, the journal Proceedings of the National Academy of Sciences reports.
“Ultimately, our study will help design better DAA drug cocktails to treat HCV,” said Loyola University Health System (LUHS) and Stritch School of Medicine (SSOM) mathematical modeller Harel Dahari, who co-led the study.
Dahari is one of five members of the Division of Hepatology at Loyola headed by Scott Cotler, who authored the study with Thomas Layden, HCV virologist Susan L. Uprichard and her doctoral graduate student Natasha Sansone, according to a Loyola statement.
“Daclatasvir not only blocks the synthesis of the viral RNA within infected cells but also secretion of infectious virus from the cells,” said Dahari.
This prediction was confirmed in Uprichard’s lab using cultured liver cells that support the entire life cycle of HCV infection.