Biomaterial Database

In silico analysis and identification of antiviral coumarin derivatives against 3-chymotrypsin-like main protease of the novel coronavirus SARS-CoV-2. 2022

Rahman Abdizadeh, and Farzin Hadizadeh, and Tooba Abdizadeh

Department of Medical Parasitology and Mycology, Faculty of Medicine, Shahrekord University of Medical Sciences, Shahrekord, Iran.

Coronavirus disease 2019 (COVID-19) is a pandemic viral disease caused by SARS-CoV-2 that generated serious damages for both the human population and the global economy. Therefore, it is currently considered as one of the most important global health problems of human societies and there is an urgent need for potent drugs or vaccines which can effectively combat this virus. The chymotrypsin-like protease (3CLpro) of SARS-CoV-2 plays a key role in the viral replication inside the host and thus is a promising drug target to design and develop effective antiviral drugs against SARS and other coronaviruses. This study evaluated some antiviral coumarin phytochemicals as potential inhibitors of coronaviruses 3CLpro by in silico approaches such as molecular docking, ADMET prediction, molecular dynamics simulation, and MM-PBSA binding energy calculation. Natural coumarin derivatives were docked to the 3CLpro of SARS-CoV-2 and for further investigation, docked to the 3CLpro of SARS-CoV and MERS-CoV. The docking scores of these natural compounds were compared with 3CLpro referenced inhibitors (ritonavir and lopinavir) and co-crystal inhibitor N3. Molecular docking studies suggested more than half of the coumarin phytochemicals had favorable interaction at the binding pocket of the coronaviruses 3CLpro and exhibited better binding affinities toward 3CLpro than ritonavir and lopinavir. Most antiviral phytochemicals interact strongly with one or both the catalytic dyad residues (His41 and Cys145) and the other key residues of SARS-CoV-2 main protease. Further, MD simulation and binding free energy calculations using MM-PBSA were carried out for three 3CLpro-coumarin complexes and 3CLpro-N3/lopinavir. The results confirmed that the 3CLpro-glycycoumarin, 3CLpro-oxypeucedanin hydrate, and 3CLpro-inophyllum P complexes were highly stable, experience fewer conformation fluctuations and share a similar degree of compactness. Also, the pharmacokinetics and drug-likeness studies showed good results for the selected coumarin phytochemicals.Therefore, the coumarin phytochemicals could be used as antiviral agents in the treatment of COVID-19 after further studies.

UI	MeSH Term	Description	Entries
D011480	Protease Inhibitors	Compounds which inhibit or antagonize biosynthesis or actions of proteases (ENDOPEPTIDASES).	Antiprotease,Endopeptidase Inhibitor,Endopeptidase Inhibitors,Peptidase Inhibitor,Peptidase Inhibitors,Peptide Hydrolase Inhibitor,Peptide Hydrolase Inhibitors,Peptide Peptidohydrolase Inhibitor,Peptide Peptidohydrolase Inhibitors,Protease Antagonist,Protease Antagonists,Antiproteases,Protease Inhibitor,Antagonist, Protease,Antagonists, Protease,Hydrolase Inhibitor, Peptide,Hydrolase Inhibitors, Peptide,Inhibitor, Endopeptidase,Inhibitor, Peptidase,Inhibitor, Peptide Hydrolase,Inhibitor, Peptide Peptidohydrolase,Inhibitor, Protease,Inhibitors, Endopeptidase,Inhibitors, Peptidase,Inhibitors, Peptide Hydrolase,Inhibitors, Peptide Peptidohydrolase,Inhibitors, Protease,Peptidohydrolase Inhibitor, Peptide,Peptidohydrolase Inhibitors, Peptide
D002918	Chymotrypsin	A serine endopeptidase secreted by the pancreas as its zymogen, CHYMOTRYPSINOGEN and carried in the pancreatic juice to the duodenum where it is activated by TRYPSIN. It selectively cleaves aromatic amino acids on the carboxyl side.	Alpha-Chymotrypsin Choay,Alphacutanée,Avazyme
D003374	Coumarins	Synthetic or naturally occurring substances related to coumarin, the delta-lactone of coumarinic acid.	1,2-Benzopyrone Derivatives,1,2-Benzopyrones,Coumarin Derivative,Coumarine,1,2-Benzo-Pyrones,Benzopyran-2-ones,Coumarin Derivatives,Coumarines,1,2 Benzo Pyrones,1,2 Benzopyrone Derivatives,1,2 Benzopyrones,Benzopyran 2 ones,Derivative, Coumarin,Derivatives, 1,2-Benzopyrone,Derivatives, Coumarin
D006801	Humans	Members of the species Homo sapiens.	Homo sapiens,Man (Taxonomy),Human,Man, Modern,Modern Man
D000086402	SARS-CoV-2	A species of BETACORONAVIRUS causing atypical respiratory disease (COVID-19) in humans. The organism was first identified in 2019 in Wuhan, China. The natural host is the Chinese intermediate horseshoe bat, RHINOLOPHUS affinis.	2019 Novel Coronavirus,COVID-19 Virus,COVID19 Virus,Coronavirus Disease 2019 Virus,SARS Coronavirus 2,SARS-CoV-2 Virus,Severe Acute Respiratory Syndrome Coronavirus 2,Wuhan Coronavirus,Wuhan Seafood Market Pneumonia Virus,2019-nCoV,2019 Novel Coronaviruses,COVID 19 Virus,COVID-19 Viruses,COVID19 Viruses,Coronavirus 2, SARS,Coronavirus, 2019 Novel,Coronavirus, Wuhan,Novel Coronavirus, 2019,SARS CoV 2 Virus,SARS-CoV-2 Viruses,Virus, COVID-19,Virus, COVID19,Virus, SARS-CoV-2,Viruses, COVID19
D000093485	COVID-19 Drug Treatment	The use of DRUGS to treat COVID19 or its symptoms.	COVID-19 Drug Therapy,COVID19 Drug Therapy,COVID19 Drug Treatment,Coronavirus Disease 2019 Drug Treatment,Coronavirus Disease-19 Drug Treatment,COVID 19 Drug Therapy,COVID 19 Drug Treatment,COVID-19 Drug Therapies,COVID19 Drug Therapies,COVID19 Drug Treatments,Coronavirus Disease 19 Drug Treatment,Drug Therapy, COVID-19,Drug Therapy, COVID19,Therapy, COVID-19 Drug,Therapy, COVID19 Drug,Treatment, COVID-19 Drug
D000998	Antiviral Agents	Agents used in the prophylaxis or therapy of VIRUS DISEASES. Some of the ways they may act include preventing viral replication by inhibiting viral DNA polymerase; binding to specific cell-surface receptors and inhibiting viral penetration or uncoating; inhibiting viral protein synthesis; or blocking late stages of virus assembly.	Antiviral,Antiviral Agent,Antiviral Drug,Antivirals,Antiviral Drugs,Agent, Antiviral,Agents, Antiviral,Drug, Antiviral,Drugs, Antiviral
D053818	Chymases	A family of neutral serine proteases with CHYMOTRYPSIN-like activity. Chymases are primarily found in the SECRETORY GRANULES of MAST CELLS and are released during mast cell degranulation.	Chymase,Chymase-1,Chymotrypsin-Like Protease,Chymotrypsin-Like Proteases,Chymase 1,Chymotrypsin Like Protease,Chymotrypsin Like Proteases
D056004	Molecular Dynamics Simulation	A computer simulation developed to study the motion of molecules over a period of time.	Molecular Dynamics Simulations,Molecular Dynamics,Dynamic, Molecular,Dynamics Simulation, Molecular,Dynamics Simulations, Molecular,Dynamics, Molecular,Molecular Dynamic,Simulation, Molecular Dynamics,Simulations, Molecular Dynamics
D061466	Lopinavir	An HIV protease inhibitor used in a fixed-dose combination with RITONAVIR. It is also an inhibitor of CYTOCHROME P-450 CYP3A.	A-157378.0,ABT 378,ABT-378,N-(4-(((2,6-dimethylphenoxy)acetyl)amino)-3-hydroxy-5-phenyl-1-(phenylmethyl)pentyl)tetrahydro-alpha-(1-methylethyl)-2-oxo-1(2H)-pydrimidineacetamide,A 157378.0,A157378.0,ABT378