Targeting the 3C Protease of Hepatitis A Virus Subgenotype IB: Virtual Screening and Identification of Potent Lead Candidates.

Hepatitis A virus (HAV) infection remains a global public health concern in both developing and developed countries. In the present study, we identified anti-HAV drugs, using AutoDock Vina Modeling software, and evaluated the compounds in vitro. Following cytotoxicity for Huh7 cells, 5 out of 10 compounds were selected. We evaluated effective HAV 3C protease inhibitors with activity against both HAV genotype IB HM175/18f and HAV genotype IIIA HA11-1299-infected human hepatoma cells. Among the five compounds, we identified only one (KCN-A-12), which had an inhibitory effect on both HAV genotype IB HM175/18f and HAV genotype IIIA HA11-1299 replication in human hepatoma Huh7 cells. KCN-A-12 has more effective inhibitory effects on the replication of HAV genotype IB HM175/18f than that of HAV genotype IIIA HA11-1299. This difference may be attributable to the fact that our discovery system depends on crystal structures from HAV 3C protease based on the HAV genotype IB HM175 strain. In conclusion, we observed that KCN-A-12 was able to inhibit HAV replication. In silico screening for HAV 3C protease inhibitors may be useful for further discovery of anti-HAV drugs.