The hope and hype of ellagic acid and urolithins as ligands of SARS-CoV-2 Nsp5 and inhibitors of viral replication.
Antiviral
microscale thermophoresis
polyphenols
urolithins
Journal
Journal of enzyme inhibition and medicinal chemistry
ISSN: 1475-6374
Titre abrégé: J Enzyme Inhib Med Chem
Pays: England
ID NLM: 101150203
Informations de publication
Date de publication:
Dec 2023
Dec 2023
Historique:
medline:
29
8
2023
pubmed:
28
8
2023
entrez:
28
8
2023
Statut:
ppublish
Résumé
Non-structural protein 5 (Nsp5) is a cysteine protease that plays a key role in SARS-CoV-2 replication, suppressing host protein synthesis and promoting immune evasion. The investigation of natural products as a potential strategy for Nsp5 inhibition is gaining attention as a means of developing antiviral agents. In this work, we have investigated the physicochemical properties and structure-activity relationships of ellagic acid and its gut metabolites, urolithins A-D, as ligands of Nsp5. Results allow us to identify urolithin D as promising ligand of Nsp5, with a dissociation constant in the nanomolar range of potency. Although urolithin D is able to bind to the catalytic cleft of Nsp5, the appraisal of its viral replication inhibition against SARS-CoV-2 in Vero E6 assay highlights a lack of activity. While these results are discussed in the framework of the available literature reporting conflicting data on polyphenol antiviral activity, they provide new clues for natural products as potential viral protease inhibitors.
Identifiants
pubmed: 37638806
doi: 10.1080/14756366.2023.2251721
pmc: PMC10464554
doi:
Substances chimiques
Antiviral Agents
0
Biological Products
0
Ellagic Acid
19YRN3ZS9P
Heterocyclic Compounds
0
Ligands
0
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Pagination
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