A Novel Small Molecule Inhibits Hepatitis C Virus Propagation in Cell Culture

• DOI: 10.1128/spectrum.00439-21
• Publication Date: 2021-07-28T14:32:01Z
• Authors: Ahmed K. Oraby; Cassandra L. Gardner; Robert F. Needle; Hassan M. Kofahi; Kylie R. Everard; Nathan G. A. Taylor; Suzette G. Rutihinda; Jacqueline P. Barry; Kensuke Hirasawa; Paris E. Georghiou; Rodney S. Russell
• Keywords: NS5B; NS2-3 protease; NS3; Viral life cycle

Hepatitis C virus (HCV) can cause acute and chronic infection that is associated with considerable liver-related morbidity mortality. In recent years, there has been a shift in the treatment paradigm discovery approval of agents target specific proteins vital for viral replication. We employed cell culture-adapted strain HCV human hepatoma-derived cells lines to test effects our novel small-molecule compound (AO13) on HCV. Virus inhibition was tested by analyzing RNA replication, protein expression, production virus-infected treated AO13. Treatment AO13 inhibited spread culture showed 100-fold reduction levels infectious production. significantly reduced level contained within fluids cellular core protein, suggesting might act late step life cycle. Finally, we observed did not affect release from infected cells. Docking studies molecular dynamics analyses suggested NS5B polymerase, however, real-time RT-PCR only an ∼2-fold presence Taken together, this study revealed consistent, but low-level antiviral effect against HCV, although mechanism action remains unclear. IMPORTANCE The curative drugs disease such as encouraged drug context other viruses which no currently exist. Since face caused pandemic, need new more apparent than ever. describe here shows modest could serve lead future development important SARS-CoV-2.