Identification of Zika virus NS2B-NS3 protease inhibitors by Structure-Based Virtual Screening and Drug Repurposing Approaches

The NS2B-NS3 protease has been identified as an attractive target for drug development against Zika virus (ZIKV) and combined drug repurposing and structure-based virtual screening has improved the development of antiviral drugs. In this study, we performed a structure-based virtual screening of 1861 Food and Administration (FDA) approved drugs available in DrugBank by the selection and docking validation of crystal structure of ZIKV NS2B-NS3 protease (PDB ID 5H4I) using Glide and DOCK 6 software. The antihistaminic chlorcyclizine (Grid score -24.8 Kcal/mol) exhibited the most promising interaction with NS2B-NS3 protease in comparison to crystallography ligand (Grid score -15.6 kcal/mol) by interaction to Tyr161 by hydrophobic interactions in the binding site of NS2B-NS3 which is recognized as an important aminoacid in substrate molecular recognition. Cytotoxicity and global antiviral activity assay in vero cells by MTT method showed that chlorcyclizine reduced the ZIKV induced cytopathic effect (EC50 of ...