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3CLpro and PLpro affinity, a docking study to fight COVID19 based on 900 compounds from PubChem and literature. Are there new drugs to be found?

Štekláč, Marek ; Zajaček, Dávid ; Bučinský, Lukáš

Journal of molecular structure, 2021-12, Vol.1245, p.130968-130968, Article 130968 [Periódico revisado por pares]

Elsevier B.V

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  • Título:
    3CLpro and PLpro affinity, a docking study to fight COVID19 based on 900 compounds from PubChem and literature. Are there new drugs to be found?
  • Autor: Štekláč, Marek ; Zajaček, Dávid ; Bučinský, Lukáš
  • Assuntos: 3CLpro ; Molecular docking ; PLpro ; PubChem ; SARS-CoV-2
  • É parte de: Journal of molecular structure, 2021-12, Vol.1245, p.130968-130968, Article 130968
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
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  • Descrição: •Docking scores of more than 900 compounds against 3CLpro and PLpro are reported.•Several compounds with high binding affinity to SARS-CoV-2 proteases are reported.•Based on their size and shape, 3CLpro and PLpro cavities bind different compounds.•Molecular dynamics simulations are necessary for final pose confirmation.•Library with acquired molecular docking data has been created (IDs, scores, etc.). The spread of a novel coronavirus SARS-CoV-2 and a resulting COVID19 disease in late 2019 has transformed into a worldwide pandemic and has effectively brought the world to a halt. Proteases 3CLpro and PLpro, responsible for proteolysis of new virions, represent vital inhibition targets for the COVID19 treatment. Herein, we report an in silico docking study of more than 860 COVID19-related compounds from the PubChem database. Molecular dynamic simulations were carried out to validate the conformation stability of compound-ligand complexes with best docking scores. The MM-PBSA approach was employed to calculate binding free energies. The comparison with ca. 50 previously reported potential SARS-CoV-2′s proteases inhibitors show a number of new compounds with excellent binding affinities. Anti-inflammatory drugs Montelukast, Ebastine and Solumedrol, the anti-migraine drug Vazegepant or the anti-MRSA pro-drug TAK-599, among many others, all show remarkable affinities to 3CLpro and with known side effects present candidates for immediate clinical trials. This study reports thorough docking scores summary of COVID19-related compounds found in the PubChem database and illustrates the asset of computational screening methods in search for possible drug-like candidates. Several yet-untested compounds show affinities on par with reported inhibitors and warrant further attention. Furthermore, the submitted work provides readers with ADME data, ZINC and PubChem IDs, as well as docking scores of all studied compounds for further comparisons. [Display omitted]
  • Editor: Elsevier B.V
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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