Impact of new cyclooxygenase 2 inhibitors on human cytomegalovirus replication in vitro.
Cytomegalovirus
anti-cyclooxygenase 2
antiviral therapy
Journal
Antiviral therapy
ISSN: 2040-2058
Titre abrégé: Antivir Ther
Pays: England
ID NLM: 9815705
Informations de publication
Date de publication:
11 2021
11 2021
Historique:
entrez:
29
4
2022
pubmed:
30
4
2022
medline:
3
5
2022
Statut:
ppublish
Résumé
Human cytomegalovirus (HCMV) is involved in complications on immunocompromised patients. Current therapeutics are associated with several drawbacks, such as nephrotoxicity. As HCMV infection affects inflammation pathways, especially prostaglandin E2 (PGE2) production via cyclooxygenase 2 enzyme (COX-2), we designed 2'-hydroxychalcone compounds to inhibit human cytomegalovirus. We first selected the most efficient new synthetic chalcones for their effect against COX-2-catalyzed PGE2. Among the selected compounds, we assessed the antiviral efficacy against different HCMV strains, such as the laboratory strain AD169 and clinical strains (naïve or multi-resistant to conventional drugs) and toxicity on human cells. The most efficient and less toxic compound (chalcone 7) was tested against HCMV in combination with other antiviral molecules: artesunate (ART), baicalein (BAI), maribavir (MBV), ganciclovir (GCV), and quercetin (QUER) using Compusyn software. Association of chalcone 7 with MBV and BAI is synergistic, antagonistic with QUER, and additive with GCV and ART. These results provide a promising search path for potential bitherapies against HCMV.
Sections du résumé
BACKGROUND
Human cytomegalovirus (HCMV) is involved in complications on immunocompromised patients. Current therapeutics are associated with several drawbacks, such as nephrotoxicity.
PURPOSE
As HCMV infection affects inflammation pathways, especially prostaglandin E2 (PGE2) production via cyclooxygenase 2 enzyme (COX-2), we designed 2'-hydroxychalcone compounds to inhibit human cytomegalovirus.
STUDY DESIGN
We first selected the most efficient new synthetic chalcones for their effect against COX-2-catalyzed PGE2.
STUDY SAMPLE
Among the selected compounds, we assessed the antiviral efficacy against different HCMV strains, such as the laboratory strain AD169 and clinical strains (naïve or multi-resistant to conventional drugs) and toxicity on human cells.
RESULTS
The most efficient and less toxic compound (chalcone 7) was tested against HCMV in combination with other antiviral molecules: artesunate (ART), baicalein (BAI), maribavir (MBV), ganciclovir (GCV), and quercetin (QUER) using Compusyn software. Association of chalcone 7 with MBV and BAI is synergistic, antagonistic with QUER, and additive with GCV and ART.
CONCLUSION
These results provide a promising search path for potential bitherapies against HCMV.
Identifiants
pubmed: 35485337
doi: 10.1177/13596535211064078
doi:
Substances chimiques
Antiviral Agents
0
Cyclooxygenase 2 Inhibitors
0
Chalcone
5S5A2Q39HX
Artesunate
60W3249T9M
Cyclooxygenase 2
EC 1.14.99.1
Dinoprostone
K7Q1JQR04M
Ganciclovir
P9G3CKZ4P5
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM