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


Awwad A. Radwan
Fares K. Alanazi

Abstract

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 druglikeness
of 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


Journal Identifiers


eISSN: 1596-9827
print ISSN: 1596-5996