Volobueva Alexandrina S, Fedorchenko Tatyana G, Lipunova Galina N, Valova Marina S, Sbarzaglia Valeriya A, Gladkikh Anna S, Kanaeva Olga I, Tolstykh Natalia A, Gorshkov Andrey N, Zarubaev Vladimir V
St. Petersburg Pasteur Institute, 14 Mira St., St. Petersburg 197101, Russia.
Postovsky Institute of Organic Synthesis, Ural Branch of the Russian Academy of Sciences, 22/20 S. Kovalevskoi St., Yekaterinburg 620108, Russia.
Pathogens. 2024 May 15;13(5):410. doi: 10.3390/pathogens13050410.
Enteroviruses (EV) are important pathogens causing human disease with various clinical manifestations. To date, treatment of enteroviral infections is mainly supportive since no vaccination or antiviral drugs are approved for their prevention or treatment. Here, we describe the antiviral properties and mechanisms of action of leucoverdazyls-novel heterocyclic compounds with antioxidant potential. The lead compound, , demonstrated low cytotoxicity along with high antioxidant and virus-inhibiting activity. A viral strain resistant to was selected, and the development of resistance was shown to be accompanied by mutation of virus-specific non-structural protein 2C. This resistant virus had lower fitness when grown in cell culture. Taken together, our results demonstrate high antiviral potential of leucoverdazyls as novel inhibitors of enterovirus replication and support previous evidence of an important role of 2C proteins in EV replication.
肠道病毒（EV）是导致人类疾病且具有多种临床表现的重要病原体。迄今为止，由于尚无获批用于预防或治疗肠道病毒感染的疫苗或抗病毒药物，因此对肠道病毒感染的治疗主要是支持性治疗。在此，我们描述了具有抗氧化潜力的新型杂环化合物白叶藤碱的抗病毒特性和作用机制。先导化合物显示出低细胞毒性以及高抗氧化和病毒抑制活性。筛选出了对白叶藤碱耐药的病毒株，并且发现耐药性的产生伴随着病毒特异性非结构蛋白2C的突变。这种耐药病毒在细胞培养中生长时适应性较低。综上所述，我们的结果表明白叶藤碱作为肠道病毒复制的新型抑制剂具有很高的抗病毒潜力，并支持了先前关于2C蛋白在肠道病毒复制中起重要作用的证据。
