Chrysin 7-O-ß-D-glucuronide, a dual inhibitor of SARS-CoV-2 3CLpro and PLpro, for the prevention and treatment of COVID-19.
Int J Antimicrob Agents
; 63(1): 107039, 2024 Jan.
Article
em En
| MEDLINE
| ID: mdl-37981073
ABSTRACT
The emergence of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) resulted in the coronavirus disease 2019 (COVID-19) pandemic. Given the advent of subvariants, there is an urgent need to develop novel drugs. The aim of this study was to find SARS-CoV-2 inhibitors from Scutellaria baicalensis Georgi targeting the proteases 3CLpro and PLpro. After screening 25 flavonoids, chrysin 7-O-ß-D-glucuronide was found to be a potent inhibitor of SARS-CoV-2 on Vero E6 cells, with half-maximal effective concentration of 8.72 µM. Surface plasmon resonance assay, site-directed mutagenesis and enzymatic activity measurements indicated that chrysin-7-O-ß-D-glucuronide inhibits SARS-CoV-2 by binding to H41 of 3CLpro, and K157 and E167 of PLpro. Hydrogen-deuterium exchange mass spectrometry analysis showed that chrysin-7-O-ß-D-glucuronide changes the conformation of PLpro. Finally, chrysin 7-O-ß-D-glucuronide was shown to have anti-inflammatory activity, mainly due to reduction of the levels of the pro-inflammatory cytokines interleukin (IL)-1ß and IL-6.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
COVID-19
Limite:
Humans
Idioma:
En
Revista:
Int J Antimicrob Agents
Ano de publicação:
2024
Tipo de documento:
Article
País de publicação:
HOLANDA
/
HOLLAND
/
NETHERLANDS
/
NL
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PAISES BAJOS
/
THE NETHERLANDS