Andouard D, Gueye R, Hantz S, Fagnère C, Liagre B, Bernardaud L, Pouget C, Duroux J L, Alain S
INSERM, CHU Limoges, RESINFIT, U1092, 27025University Limoges, Limoges, France.
National Reference Center for Herpesviruses, Laboratoire de Bactériologie-Virologie-Hygiène, 36715CHU Limoges, Limoges, France.
Antivir Ther. 2021 Nov;26(6-8):117-125. doi: 10.1177/13596535211064078. Epub 2021 Nov 29.
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.
人巨细胞病毒（HCMV）与免疫功能低下患者的并发症有关。目前的治疗方法存在一些缺点，如肾毒性。
由于HCMV感染会影响炎症途径，特别是通过环氧合酶2（COX-2）产生前列腺素E2（PGE2），我们设计了2'-羟基查尔酮化合物来抑制人巨细胞病毒。
我们首先选择了对COX-2催化的PGE2作用最有效的新型合成查尔酮。
在所选化合物中，我们评估了其对不同HCMV毒株的抗病毒效果，如实验室毒株AD169和临床毒株（对传统药物未感染或多重耐药）以及对人细胞的毒性。
使用Compusyn软件，将最有效且毒性较小的化合物（查尔酮7）与其他抗病毒分子联合用于抗HCMV测试：青蒿琥酯（ART）、黄芩素（BAI）、马里巴韦（MBV）、更昔洛韦（GCV）和槲皮素（QUER）。查尔酮7与MBV和BAI联合具有协同作用，与QUER联合具有拮抗作用，与GCV和ART联合具有相加作用。
这些结果为潜在的抗HCMV联合治疗提供了一条有前景的探索途径。
