Background:
3C-like protease also called the main protease is an essential enzyme for the
completion of the life cycle of Middle East Respiratory Syndrome Coronavirus. In our study we predicted
compounds which are capable of inhibiting 3C-like protease, and thus inhibit the lifecycle of
Middle East Respiratory Syndrome Coronavirus using in silico methods.
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Methods: Lead like compounds and drug molecules which are capable of inhibiting 3C-like protease
was identified by structure-based virtual screening and ligand-based virtual screening method. Further,
the compounds were validated through absorption, distribution, metabolism and excretion filtering.
Results:
Based on binding energy, ADME properties, and toxicology analysis, we finally selected 3
compounds from structure-based virtual screening (ZINC ID: 75121653, 41131653, and 67266079)
having binding energy -7.12, -7.1 and -7.08 Kcal/mol, respectively and 5 compounds from ligandbased
virtual screening (ZINC ID: 05576502, 47654332, 04829153, 86434515 and 25626324) having
binding energy -49.8, -54.9, -65.6, -61.1 and -66.7 Kcal/mol respectively. All these compounds have
good ADME profile and reduced toxicity. Among eight compounds, one is soluble in water and remaining
7 compounds are highly soluble in water. All compounds have bioavailability 0.55 on the
scale of 0 to 1. Among the 5 compounds from structure-based virtual screening, 2 compounds showed
leadlikeness. All the compounds showed no inhibition of cytochrome P450 enzymes, no blood-brain
barrier permeability and no toxic structure in medicinal chemistry profile. All the compounds are not a
substrate of P-glycoprotein.
Our predicted compounds may be capable of inhibiting 3C-like protease but need some
further validation in wet lab.
Binding Ensembles of p53-MDM2 Peptide Inhibitors by Combining Bayesian Inference and Atomistic Simulations