Search for structural scaffolds against SARS-COV-2 Mpro: an <i>in silico</i> study

Abstract

The emergence of the deadly SARS-CoV-2, the etiologic agent of COVID-19 towards the end of the fourth quarter of 2019 has necessitated intensive research towards the development of drugs and vaccine that can combat the disease. Consequently, we conducted molecular docking of the e-Drug3D library using London dG and Affinity dG as scoring algorithms for common structural scaffolds in drug molecules with strong binding affinities towards SARS-CoV-2 M^pro. 15 drug molecules forming about 0.8% of the library bound strongly to the target protein, which gave rise to Two potential structural scaffolds: (4S,4aR,5aR,12aS)-4-(dimethylamino)-10,12,12a-trihydroxy-1,11-dioxo-1,4,4a,5,5a,6,11,12a-octahydro-2-tetracenecarboxamide and the stilbenoid-like structure. These scaffolds could serve as potential starting points in the structure-based design of anti-SARS-CoV-2 drugs.