Comparative evaluation of flavonoids reveals the superiority and promising inhibition activity of silibinin against SARS-CoV-2.
Phytother Res
; 36(7): 2921-2939, 2022 Jul.
Article
em En
| MEDLINE
| ID: mdl-35596627
ABSTRACT
Flavonoids are phenolic compounds naturally found in plants and commonly consumed in diets. Herein, flavonoids were sequentially evaluated by a comparative in silico study associated with systematic literature search. This was followed by an in vitro study and enzyme inhibition assays against vital SARS-CoV-2 proteins including spike (S) protein, main protease (Mpro ), RNA-dependent RNA-polymerase (RdRp), and human transmembrane serine protease (TMPRSS2). The results obtained revealed 10 flavonoids with potential antiviral activity. Out of them, silibinin showed promising selectivity index against SARS-CoV-2 in vitro. Screening against S protein discloses the highest inhibition activity of silibinin. Mapping the activity of silibinin indicated its excellent binding inhibition activity against SARS-CoV-2 S protein, Mpro and RdRP at IC50 0.029, 0.021, and 0.042 µM, respectively, while it showed no inhibition activity against TMPRSS2 at its IC50(SARS-CoV-2) . Silibinin was tested safe on human mammalian cells at >7-fold its IC50(SARS-CoV-2) . Additionally, silibinin exhibited >90% virucidal activity at 0.031 µM. Comparative molecular docking (MD) showed that silibinin possesses the highest binding affinity to S protein and RdRP at -7.78 and -7.15 kcal/mol, respectively. MDs showed that silibinin exhibited stable interaction with key amino acids of SARS-CoV-2 targets. Collectively, silibinin, an FDA-approved drug, can significantly interfere with SARS-CoV-2 entry and replication through multi-targeting activity.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
SARS-CoV-2
/
Tratamento Farmacológico da COVID-19
Tipo de estudo:
Systematic_reviews
Limite:
Humans
Idioma:
En
Revista:
Phytother Res
Ano de publicação:
2022
Tipo de documento:
Article