Exploring the Traditional Chinese Medicine (TCM) database chemical space to target I7L protease from monkeypox virus using molecular screening and simulation approaches

Abstract

ABSTRACT In the current study, we used molecular screening and simulation approaches to target I7L protease from monkeypox virus (mpox) from the Traditional Chinese Medicines (TCM) database. Using molecular screening, only four hits TCM27763, TCM33057, TCM34450 and TCM31564 demonstrated better pharmacological potential than TTP6171 (control). Binding of these molecules targeted Trp168, Asn171, Arg196, Cys237, Ser240, Trp242, Glu325, Ser326, and Cys328 residues and may affect the function of I7L protease in in vitro assay. Moreover, molecular simulation revealed stable dynamics, tighter structural packing and less flexible behaviour for all the complexes. We further reported that the average hydrogen bonds in TCM27763, TCM33057, TCM34450 and TCM31564I7L complexes remained higher than the control drug. Finally, the BF energy results revealed −62.60 ± 0.65 for the controlI7L complex, for the TCM27763I7L complex −71.92 ± 0.70 kcal/mol, for the TCM33057I7L complex the BF energy was −70.94 ± 0.70 kcal/mol, for the TCM34450I7L the BF energy was −69.94 ± 0.85 kcal/mol while for the TCM31564I7L complex the BF energy was calculated to be −69.16 ± 0.80 kcal/mol. Although, we used stateoftheart computational methods, these are theoretical insights that need further experimental validation.