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The NS3 protein plays an important role in HCV replication, where its N-terminal domain acts as a protease to process most of the viral polypeptides. In addition, this protein also functions as an RNA helicase and NTPase and triggers liver fibrosis which accelerates the development of liver disease. Resistance-associated substitution (RAS) is commonly detected in failed DAA regimens. RAS has been identified in proteins involved in HCV infection, one of which is NS3. Thus, this study has a design to identify natural compounds that are able to target the HCV NS3 protein. To identify natural compounds, a ligand-based and structure-based pharmacophore model to the cavity of the active protein site was generated after virtual screening and molecular docking. Three compounds namely stigmasterol, gamma mangostin, and erycristagallin have been found as HCV antiviral candidates that target the NS3 protein with a lower binding affinity than the original ligand. Based on ADMET analysis, the three compounds have high absorption in the small intestine. Analysis of the cytotoxicity of stigmasterol compounds did not have the potential to be mutagenic. The LD50 value of stigmasterol is also lower than other compounds. However, the stigmasterol compound has a lower MRTD.


HCV NS3 molecular docking pharmacophore modeling

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Rahayu R, Erlina L, Ratnoglik SL, Yasmon A, Fadilah, Paramita RI. Identification of Antiviral Compounds against Hepatitis C Virus (HCV) targeting NS3 protein by Pharmacophore Modeling, Molecular Docking, and ADMET Approach. EKSAKTA [Internet]. 2023Oct.23 [cited 2023Dec.2];23(04):523-36. Available from:


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