In silico studies on novel inhibitors of MERS-CoV: Structure-based pharmacophore modeling, database screening and molecular docking

Purpose: To search for novel scaffolds as potential inhibitors of 3CLpro protease enzyme and as antiviral drugs.Methods: NCI database was screened using structure-based pharmacophore modeling, database screening and molecular docking. Also, Lipininski’s rule of 5 was applied in order to test the druglikenessof the retrieved compound. Pharmacophore modelling and subsequent post-docking analyses were used for comparison of the binding mode of the retrieved hits with that of the x-ray inhibitor, R30, against MERS-CoV 3CLpro enzyme.Results: Five compounds were identified as potential agents for the treatment of corona virus, MERSCoV, which showed similar binding to MERS-CoV 3CLpro like that of the x-ray inhibitor, R30. As protease enzyme plays an indispensable role during virus life cycle, CoV 3CLpro has been reported as a highly validated drug target and it is considered viable for the design of broad spectrum inhibitors. The selected five hit compounds bind to MERS-CoV 3CLpro in a manner similar to that of the x-ray inhibitor, R30, and showed pharmacophore-fit and docking score values higher than those of R30, MERS-CoV 3CLpro-inhibitor.Conclusion: The retrieved five hits are proposed as new scaffolds for further evaluation and optimization of their activity against MERS-CoV.Keywords: MERS-CoV pharmacophore, Molecular docking, Protease enzyme, X-ray inhibitor