Dual inhibition of COVID-19 spike glycoprotein and main protease 3CLpro by Withanone from Withania somnifera
| Autor: | Vishal Shivalingappa Patil, Sanjay H. Deshpande, Shamanand Mallapur, Vrushabh B. Hupparage, Ajay P. Malgi, Sathgowda A. Patil |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
Glycosylation
medicine.medical_treatment Druggability Withania somnifera (Linn.) Dunal Withania somnifera 030226 pharmacology & pharmacy 01 natural sciences 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine medicine Pharmacology (medical) spike glycoprotein Pharmacology chemistry.chemical_classification Protease biology SARS-CoV-2 main protease 3CLpro Active site COVID-19 dynamics biology.organism_classification Withanone antiviral 0104 chemical sciences 010404 medicinal & biomolecular chemistry Complementary and alternative medicine chemistry Biochemistry Docking (molecular) docking biology.protein Original Article Glycoprotein PubChem |
| Zdroj: | Chinese Herbal Medicines |
| ISSN: | 1674-6384 |
| Popis: | Objective To identify the safe and effective natural inhibitors of spike glycoprotein and main protease 3CLpro using potential natural antiviral compounds which are studied under various animal models and viral cell lines. Methods First, compounds were retrieved from the PubChem database and predicted for their druggability using the MolSoft web server, and compounds having drug-like property were predicted for major adverse drug reactions like cardiotoxicity, hepatotoxicity, arrhythmia, myocardial infarction, and nephrotoxicity using ADVERpred. Docking of nontoxic antiviral compounds with spike glycoprotein and main protease 3CLpro was performed using AutoDock vina by PyRx 0.8 version. The stability of compound-protein interactions was checked by molecular dynamic (MD) simulation using Schrodinger Desmond software. Results Based on the druggable and nontoxic profile, nine compounds were selected. Among them, Withanone from Withania somnifera showed the highest binding affinity and best fit at active sites 1 of spike glycoprotein (glycosylation site) and main protease 3CLpro via interacting with active site amino acid residues before and after MD simulation at 50 ns. Withanone, which may reduce the glycosylation of SARS-CoV-2 via interacting with Asn343 and inhibit viral replication. Conclusion The current study reports Withanone as a non-toxic antiviral against SARS-CoV-2 and serve as a potential lead hit for further experimental validation. |
| Databáze: | OpenAIRE |
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