Impact of new cyclooxygenase 2 inhibitors on human cytomegalovirus replication in vitro.

Abstract

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.

• Authors: D Andouard, R Gueye, S Hantz, C Fagnère, B Liagre, L Bernardaud, C Pouget, J L Duroux, S Alain
• Journal: Antiviral therapy (Antivir Ther) Vol. 26 Issue 6-8 Pg. 117-125 (11 2021) ISSN: 2040-2058 [Electronic] England
• PMID: 35485337 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Antiviral Agents
• Cyclooxygenase 2 Inhibitors
• Chalcone
• Artesunate
• Cyclooxygenase 2
• Dinoprostone
• Ganciclovir

Topics

• Antiviral Agents (pharmacology)
• Artesunate (pharmacology)
• Chalcone (pharmacology)
• Cyclooxygenase 2 (pharmacology)
• Cyclooxygenase 2 Inhibitors (pharmacology)
• Cytomegalovirus
• Dinoprostone (pharmacology)
• Ganciclovir (pharmacology)
• Humans