Sandenon Seteyen Anne-Laure, Guiraud Pascale, Gasque Philippe, Girard-Valenciennes Emmanuelle, Sélambarom Jimmy
Unité de Recherche Etudes Pharmaco-Immunologiques (UR-EPI), Université de La Réunion, 97400 Saint-Denis, France.
Centre Hospitalier Universitaire de La Réunion, Laboratoire d'Immunologie Clinique et Expérimentale de la Zone Océan Indien (LICE-OI), Pôle de Biologie, 97400 Saint-Denis, France.
Pharmaceuticals (Basel). 2023 Aug 9;16(8):1125. doi: 10.3390/ph16081125.
O'nyong-nyong virus (ONNV) is a member of the reemerging arthritogenic alphaviruses that cause chronic debilitating polyarthralgia and/or polyarthritis via their tropism for the musculoskeletal system. Thus, the discovery of dual antiviral and anti-inflammatory drugs is a great challenge in this field. We investigated the effects of the common plant-derived alkaloids berberine (isoquinoline), matrine (quinolizidine), and tabersonine (indole) at a non-toxic concentration (10 μM) on a human fibroblast cell line (HS633T) infected by ONNV (MOI 1). Using qRT-PCR analyses, we measured the RNA levels of the gene coding for the viral proteins and for the host cell immune factors. These alkaloids demonstrated multifocal effects by the inhibition of viral replication, as well as the regulation of the type-I interferon antiviral signaling pathway and the inflammatory mediators and pathways. Berberine and tabersonine proved to be the more valuable compounds. The results supported the proposal that these common alkaloids may be useful scaffolds for drug discovery against arthritogenic alphavirus infection.
奥尼永永病毒（ONNV）是重新出现的致关节炎甲病毒属的成员，通过对肌肉骨骼系统的嗜性导致慢性使人衰弱的多关节痛和/或多关节炎。因此，发现兼具抗病毒和抗炎作用的药物是该领域的一大挑战。我们研究了常见的植物源生物碱黄连素（异喹啉）、苦参碱（喹诺里西啶）和长春花碱（吲哚）在无毒浓度（10 μM）下对感染ONNV（感染复数为1）的人成纤维细胞系（HS633T）的影响。通过qRT-PCR分析，我们测量了编码病毒蛋白和宿主细胞免疫因子的基因的RNA水平。这些生物碱通过抑制病毒复制以及调节I型干扰素抗病毒信号通路和炎症介质及通路表现出多方面的作用。黄连素和长春花碱被证明是更有价值的化合物。结果支持了这些常见生物碱可能是用于发现抗致关节炎甲病毒感染药物的有用骨架的提议。
