Identification of Potent Hepatitis C Virus RdRp Inhibitors by Structure Based Drug Designing

Hepatitis C, the silent disease caused by Hepatitis C virus (HCV) is a chronic health infection globally. HCV causes permanent hepatic cirrhosis and carcinoma in humans. WHO estimated about 3 million incidents of HCV infection around the world. Multiple variant genotypes along with the development of Quasi-species limited the efficacy of drugs used for the treatment of HCV infections. This heterogeneity of the virus hampered the drug development against them. The virus hosts many structural and non-structural (NS) proteins. NS5B is a non-structural protein with a unique structure and function. The protein is a RNA dependent RNA polymerase (RdRp) responsible for building the vital genetic component of the virus. Inhibition of NS5B stops viral replication and propagation. The major role played by RdRP makes it a preferential target for anti-HCV drug development. An association of docking and rescoring studies was performed to 24 compounds derived from various plant sources to estimate their activity against HCV NS5B RdRp. Based on the docking characterization and ADMET properties andrographolide, esculetin, columbin and tinosporide were identified as they showed greater potency against HCV NS5B RdRp. However, based on hepato bioactive spectrum and ADMET score, andrographolide from Andrographuis paniculata emerged as a strong contender with lead like characteristics acting as a promising drug candidate.