G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Sciences, 690022 Vladivostok, Russia.
G.P. Somov Institute of Epidemiology and Microbiology, Far-Eastern Branch of the Russian Academy of Sciences, 690087 Vladivostok, Russia.
Mar Drugs. 2020 Nov 5;18(11):550. doi: 10.3390/md18110550.
Herpes simplex virus type 1 (HSV-1) is one of the most prevalent pathogens worldwide requiring the search for new candidates for the creation of antiherpetic drugs. The ability of sea urchin spinochromes-echinochrome A (EchA) and its aminated analogues, echinamines A (EamA) and B (EamB)-to inhibit different stages of HSV-1 infection in Vero cells and to reduce the virus-induced production of reactive oxygen species (ROS) was studied. We found that spinochromes exhibited maximum antiviral activity when HSV-1 was pretreated with these compounds, which indicated the direct effect of spinochromes on HSV-1 particles. EamB and EamA both showed the highest virucidal activity by inhibiting the HSV-1 plaque formation, with a selectivity index (SI) of 80.6 and 50.3, respectively, and a reduction in HSV-1 attachment to cells (SI of 8.5 and 5.8, respectively). EamA and EamB considerably suppressed the early induction of ROS due to the virus infection. The ability of the tested compounds to directly bind to the surface glycoprotein, gD, of HSV-1 was established in silico. The dock score of EchA, EamA, and EamB was -4.75, -5.09, and -5.19 kcal/mol, respectively, which correlated with the SI of the virucidal action of these compounds and explained their ability to suppress the attachment and penetration of the virus into the cells.
单纯疱疹病毒 1 型 (HSV-1) 是全球最普遍的病原体之一,需要寻找新的候选药物来治疗疱疹。本研究旨在探讨海胆视黄质-棘皮酮 A (EchA) 及其氨基类似物,棘皮胺 A (EamA) 和 B (EamB) 抑制 Vero 细胞中 HSV-1 感染不同阶段和降低病毒诱导活性氧 (ROS) 产生的能力。我们发现,当用这些化合物预处理 HSV-1 时,海胆视黄质表现出最大的抗病毒活性,这表明海胆视黄质对 HSV-1 颗粒具有直接作用。EamB 和 EamA 均通过抑制 HSV-1 蚀斑形成表现出最高的病毒杀灭活性,其选择性指数 (SI) 分别为 80.6 和 50.3,并且降低 HSV-1 对细胞的附着 (SI 分别为 8.5 和 5.8)。EamA 和 EamB 可显著抑制因病毒感染而早期诱导的 ROS。通过计算机模拟确定了测试化合物与 HSV-1 表面糖蛋白 gD 直接结合的能力。EchA、EamA 和 EamB 的对接评分分别为-4.75、-5.09 和-5.19 kcal/mol,这与这些化合物的病毒杀灭作用的 SI 相关,并解释了它们抑制病毒附着和进入细胞的能力。