RESUMO
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.
Assuntos
COVID-19 , Humanos , SARS-CoV-2 , Glucuronídeos/farmacologia , Cisteína Endopeptidases/química , Inibidores de Proteases/farmacologia , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Antivirais/farmacologia , Antivirais/uso terapêutico , Antivirais/química , Simulação de Acoplamento MolecularRESUMO
A novel and efficient 2''-O-glycosyltransferase ZjOGT38 was identified from Ziziphus jujuba. It could regio-selectively glycosylate 2-hydroxyflavanone C-glycosides. ZjOGT38 allowed de novo biosynthesis of isovitexin 2''-O-glucoside in E. coli.