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1.
Molecules ; 27(5)2022 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-35268738

RESUMO

A new flavonoid, Jusanin, (1) has been isolated from the aerial parts of Artemisia commutata. The chemical structure of Jusanin has been elucidated using 1D, 2D NMR, and HR-Ms spectroscopic methods to be 5,2',4'-trihydroxy-6,7,5'-trimethoxyflavone. Being new in nature, the inhibition potential of 1 has been estimated against SARS-CoV-2 using different in silico techniques. Firstly, molecular similarity and fingerprint studies have been conducted for Jusanin against co-crystallized ligands of eight different SARS-CoV-2 essential proteins. The studies indicated the similarity between 1 and X77, the co-crystallized ligand SARS-CoV-2 main protease (PDB ID: 6W63). To confirm the obtained results, a DFT study was carried out and indicated the similarity of (total energy, HOMO, LUMO, gap energy, and dipole moment) between 1 and X77. Accordingly, molecular docking studies of 1 against the target enzyme have been achieved and showed that 1 bonded correctly in the protein's active site with a binding energy of -19.54 Kcal/mol. Additionally, in silico ADMET in addition to the toxicity evaluation of Jusanin against seven models have been preceded and indicated the general safety and the likeness of Jusanin to be a drug. Finally, molecular dynamics simulation studies were applied to investigate the dynamic behavior of the Mpro-Jusanin complex and confirmed the correct binding at 100 ns. In addition to 1, three other metabolites have been isolated and identified to be сapillartemisin A (2), methyl-3-[S-hydroxyprenyl]-cumarate (3), and ß-sitosterol (4).


Assuntos
Artemisia , Proteases 3C de Coronavírus , Flavonoides , SARS-CoV-2 , Animais , Humanos , Masculino , Ratos , Artemisia/química , Artemisia/metabolismo , Sítios de Ligação , Domínio Catalítico , Proteases 3C de Coronavírus/antagonistas & inibidores , Proteases 3C de Coronavírus/metabolismo , COVID-19/patologia , COVID-19/virologia , Teoria da Densidade Funcional , Flavonoides/química , Flavonoides/isolamento & purificação , Flavonoides/metabolismo , Flavonoides/farmacologia , Dose Letal Mediana , Conformação Molecular , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , SARS-CoV-2/enzimologia , SARS-CoV-2/isolamento & purificação , Pele/efeitos dos fármacos , Pele/patologia
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