Biolatti Matteo, Blangetti Marco, D'Arrigo Giulia, Spyrakis Francesca, Cappello Paola, Albano Camilla, Ravanini Paolo, Landolfo Santo, De Andrea Marco, Prandi Cristina, Dell'Oste Valentina
Department of Public Health and Pediatric Sciences, University of Turin, 10126 Turin, Italy.
Department of Chemistry, University of Turin, 10125 Turin, Italy.
Microorganisms. 2020 May 10;8(5):703. doi: 10.3390/microorganisms8050703.
The human cytomegalovirus (HCMV) is a widespread pathogen and is associated with severe diseases in immunocompromised individuals. Moreover, HCMV infection is the most frequent cause of congenital malformation in developed countries. Although nucleoside analogs have been successfully employed against HCMV, their use is hampered by the occurrence of serious side effects. There is thus an urgent clinical need for less toxic, but highly effective, antiviral drugs. Strigolactones (SLs) are a novel class of plant hormones with a multifaceted activity. While their role in plant-related fields has been extensively explored, their effects on human cells and their potential applications in medicine are far from being fully exploited. In particular, their antiviral activity has never been investigated. In the present study, a panel of SL analogs has been assessed for antiviral activity against HCMV. We demonstrate that TH-EGO and EDOT-EGO significantly inhibit HCMV replication in vitro, impairing late protein expression. Moreover, we show that the SL-dependent induction of apoptosis in HCMV-infected cells is a contributing mechanism to SL antiviral properties. Overall, our results indicate that SLs may be a promising alternative to nucleoside analogs for the treatment of HCMV infections.
人类巨细胞病毒(HCMV)是一种广泛传播的病原体,与免疫功能低下个体的严重疾病相关。此外,HCMV感染是发达国家先天性畸形最常见的原因。尽管核苷类似物已成功用于对抗HCMV,但其使用因严重副作用的出现而受到阻碍。因此,临床上迫切需要毒性较小但高效的抗病毒药物。独脚金内酯(SLs)是一类具有多方面活性的新型植物激素。虽然它们在植物相关领域的作用已被广泛研究,但其对人类细胞的影响及其在医学上的潜在应用远未得到充分开发。特别是,它们的抗病毒活性从未被研究过。在本研究中,一组SL类似物已被评估其对HCMV的抗病毒活性。我们证明TH-EGO和EDOT-EGO在体外显著抑制HCMV复制,损害晚期蛋白表达。此外,我们表明HCMV感染细胞中SL依赖性凋亡诱导是SL抗病毒特性的一个促成机制。总体而言,我们的结果表明,SLs可能是治疗HCMV感染的核苷类似物的有前途的替代品。