Ugonin J Acts as a SARS-CoV-2 3C-like Protease Inhibitor and Exhibits Anti-inflammatory Properties.
3CL protease inhibitor
COVID-19
SARS-CoV-2
lung inflammation
ugonin J
Journal
Frontiers in pharmacology
ISSN: 1663-9812
Titre abrégé: Front Pharmacol
Pays: Switzerland
ID NLM: 101548923
Informations de publication
Date de publication:
2021
2021
Historique:
received:
03
06
2021
accepted:
13
08
2021
entrez:
13
9
2021
pubmed:
14
9
2021
medline:
14
9
2021
Statut:
epublish
Résumé
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection causes severe "flu-like" symptoms that can progress to acute respiratory distress syndrome (ARDS), pneumonia, renal failure, and death. From the therapeutic perspective, 3-chymotrypsin-like protein (3CLpro) is a plausible target for direct-acting antiviral agents because of its indispensable role in viral replication. The flavonoid ugonin J (UJ) has been reported to have antioxidative and anti-inflammatory activities. However, the potential of UJ as an antiviral agent remains unexplored. In this study, we investigated the therapeutic activity of UJ against SARS-CoV-2 infection. Importantly, UJ has a distinct inhibitory activity against SARS-CoV-2 3CLpro, compared to luteolin, kaempferol, and isokaempferide. Specifically, UJ blocks the active site of SARS-CoV-2 3CLpro by forming hydrogen bonding and van der Waals interactions with H163, M165 and E166, G143 and C145, Q189, and P168 in subsites S1, S1', S2, and S4, respectively. In addition, UJ forms strong, stable interactions with core pharmacophore anchors of SARS-CoV-2 3CLpro in a computational model. UJ shows consistent anti-inflammatory activity in inflamed human alveolar basal epithelial A549 cells. Furthermore, UJ has a 50% cytotoxic concentration (CC
Identifiants
pubmed: 34512347
doi: 10.3389/fphar.2021.720018
pii: 720018
pmc: PMC8427442
doi:
Types de publication
Journal Article
Langues
eng
Pagination
720018Informations de copyright
Copyright © 2021 Chiou, Lu, Hsu, Chang, Chin, Liu, Lo, Wu, Yang and Huang.
Déclaration de conflit d'intérêts
Author YW was employed by the company Arjil Biotech Holding Company Limited. The remaining authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.
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