Virtual screening based on molecular docking of possible inhibitors of Covid-19 main protease
| Autor: | João Batista de Andrade Neto, Cecília Rocha da Silva, Bruno C. Cavalcanti, Jacilene Silva, Emanuelle Machado Marinho, Emmanuel Silva Marinho, Hélio Vitoriano Nobre Júnior |
|---|---|
| Jazyk: | angličtina |
| Rok vydání: | 2020 |
| Předmět: |
0301 basic medicine
Ruxolitinib medicine.medical_treatment In silico 030106 microbiology Drug Evaluation Preclinical Computational biology Cysteine Proteinase Inhibitors medicine.disease_cause Antiviral Agents Molecular Docking Simulation Microbiology Article 03 medical and health sciences Drug Discovery medicine Humans Protease Inhibitors Coronavirus 3C Proteases Coronavirus Virtual screening Binding Sites Protease Inhibitors SARS-CoV-2 Drug discovery business.industry COVID-19 COVID-19 Drug Treatment Cysteine Endopeptidases 030104 developmental biology Infectious Diseases Docking (molecular) Molecular docking business medicine.drug |
| Zdroj: | Microbial Pathogenesis |
| ISSN: | 0882-4010 |
| DOI: | 10.1016/j.micpath.2020.104365 |
| Popis: | Coronavirus (COVID-19) is an enveloped RNA virus that is diversely found in humans and that has now been declared a global pandemic by the World Health Organization. Thus, there is an urgent need to develop effective therapies and vaccines against this disease. In this context, this study aimed to evaluate in silico the molecular interactions of drugs with therapeutic indications for treatment of COVID-19 (Azithromycin, Baricitinib and Hydroxychloroquine) and drugs with similar structures (Chloroquine, Quinacrine and Ruxolitinib) in docking models from the SARS-CoV-2 main protease (M-pro) protein. The results showed that all inhibitors bound to the same enzyme site, more specifically in domain III of the SARS-CoV-2 main protease. Therefore, this study allows proposing the use of baricitinib and quinacrine, in combination with azithromycin; however, these computer simulations are just an initial step for conceiving new projects for the development of antiviral molecules. Highlights • The analysis of molecular docking simulations showed that all inhibitors bound to the same enzyme site. • All inhibitors bound in domain III of the SARS-CoV-2 main protease. • Were identified in the molecular docking simulations, classified as Hydrogen Bond Strongly Covalent with baricitinib (Asp197 and Leu287), chloroquine (Tyr239), and quinacrine (Tyr239). • Were identified in the molecular docking simulations, classified as Hydrogen Bond Moderate Mostly Electrostatic with baricitinib (Lys137), azithromycin (Leu272), hydroxychloroquine (Lys137 e Tyr237), and ruxolitinib (Lys137 |
| Databáze: | OpenAIRE |
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