Background: Hepatitis C is an infectious liver disease with high mortality rate which is caused by Hepatitis C virus. Several treatment methods have been applied to combat this deadly virus including interferons, vaccine and direct acting antivirals (DAAs). However, the later shows promising effects in HCV treatment with lower adverse effect. Specifically, the DAAs target the non-structural proteins (NS3 and NS5B). Purpose: The objective of the present study is to hypothesize an alternative antiviral inhibitor for HCV from the available other antivirals. Methods: Computation of 2D molecular descriptors for the selected antiviral inhibitors followed by clustering the descriptor features. The closely clustered compounds were subjected to the interaction studies against the HCV target protein to validate the cluster result. Results and discussion: The clustering result showed that indinavir (HIV inhibitor) and AT130 (HBV inhibitor) molecule are close to the HCV inhibitor. The indinavir complexed with NS3 protein shows -5.33 kcal/mol and AT-130 complexed with NS5B protein possess the binding energy of -8.87 kcal/mol. The docking interaction study indicated a better binding affinity than other viral inhibitors. Conclusion: From the descriptor based feature similarity analysis and the interaction study, it can be concluded that indinavir and AT-130 could be a potential alternative agent for HCV treatment. (C) 2017 Elsevier Inc. All rights reserved.