In-silico Screening of Some Important Bioactive Compounds as Potential Inhibitors of 3CLpro Protein of SARS-CoV-2 and MERS-CoV Virus

Abstract

Background: Coronavirus (SARS-CoV-2), the leading cause of the epidemic in 2019, also known as COVID-19, has raised ongoing global concerns. The most favourable target protein for this flu is 3CLpro (conserved 3-chymotrypsin-like protease), also known as Mpro. Covaxin and Covishield vaccination is going in India. Remdesivir, as well as some antimalarial drugs such as Hydroxychloroquine and Chloroquine, are used for extreme necessity. However, Hydroxychloroquine and Chloroquine and their derivatives are not convenient for those who are suffering from hypertension, diabetes, cardiac arrest, and many more. 
 Objective: Here, we choose some bioactive compounds for docking studies with the Mpro of SARS CoV2 and MERS as it is used as the primary target for a comparative study. 
 Methods: The docking process was carried out by preparing both 3CLpro proteins, i.e., 2YNA and 6LU7, and then the ligand molecules were downloaded from Pubchem, DrugBank, and Zinc15 databases. Furthermore, SwissAdme and pkCSM software were used for the determination of toxicity and Pharmacokinetic properties (ADMET) properties. Lastly, docking was carried out by the Autodock version 4.2 program, and the docking score was compared to the reference inhibitor Ritonavir. 
 Results: Among 17 bioactive compounds used for docking studies, Quercetin, Trans-Resveratol, Kaemferol, and Theaflavin have top, binding affinity for target proteins, i.e., Theaflavin (-14.35 kcal/mol), Quercetin (-11.88kcal/mol), Kaempferol (-9.3 kcal/mol) and Trans-Resveratol (-9.31 kcal/mol) and also obey Lipinski's rule which makes them potential drug candidate against Covid-19 virus. Hence, the application of these plant-based bioactive compounds alone or along with scheduled vaccination may be the best therapeutic approach in the current scenario.

An in silico approach to develop potential therapies against Middle East Respiratory Syndrome Coronavirus (MERS-CoV)

“…In addition, plant-derived phytochemicals, including Kaempferol (−9.3 kcal/mol), Resveratrol (−9.31 kcal/mol), Quercetin (−11.88 kcal/mol), and Theaflavin (−14.35 kcal/mol), showed the highest binding affinity for the 3CL pro protein of MERS-CoV. However, the relevant study lacks an analysis of the binding mode stability of the docked complex through molecular docking simulation [ 99 ]. Conversely, all the hit compounds in our study, including Kihadanin B, Robustaflavone, and 3-beta-O-( trans -p-Coumaroyl) maslinic acid, exhibited the structural stability and firmness of the docked complexes over 100 ns of molecular dynamics simulation.…”