Abstract

Herpes viruses (HSV) are among the most common viruses that infect humans. They cause blisters and inflammation of the oral and genital mucosa as well as severe symptoms such as blindness, hearing impairment and fatal encephalitis. Although acyclovir (ACV) and its derivatives are highly effective in treating recurrent lytic infections, the emergence of resistant strains remains a concern. In this study, the in vitro anti-herpetic activity of a hydroalcoholic extract obtained from the brown seaweed Sargassum fluitans, collected from strandings in Cuba, was evaluated. The hydroalcoholic extract was not cytotoxic in Vero cells (CC₅₀ >5000 µg mL^-1) and inhibited replication of HSV-1 (ACV-susceptible and -resistant) and HSV-2 (ACV-resistant) strains with EC₅₀ of 271.66, 403.62 and 14.99 µg mL^-1 respectively. In addition, first studies about mechanism of action were evaluated with ACV-sensitive HSV-1 model. The extract showed strong inhibition when pre-incubated with the virus and when the extract and virus were added simultaneously on the cells. The protection of Vero cells during the post-infection assay was very effective up to 1 h. A high resolution UPLC/MS-MS analysis detected 139 compounds, of which 44 were identified. In silico analysis was performed to determine the putative interaction sites of two flavones of interest identified in the extract with the viral glycoprotein D (gD). Molecular docking analysis revealed that takakin and tectorigenin mainly interact with the gD protein active center through hydrophobic interactions (Leu44, Pro50, Thr174, Lys169, Tyr208, Gln209) while hydrogen bonding interactions are less abundant (Ser43, Asp46, Lys169, Tyr208). This research represents a contribution to the valorization of S. fluitans as a source of anti-herpetic compounds in the context of recurrent and abundant seaweed strandings.

中文翻译：

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从马尾藻 (Børgesen) Børgesen 中提取的化合物的体外抗疱疹活性。水醇提取物中潜在抗病毒分子的鉴定和计算机评估

摘要

疱疹病毒（HSV）是感染人类的​​最常见病毒之一。它们会引起口腔和生殖器粘膜出现水泡和炎症，以及失明、听力障碍和致命性脑炎等严重症状。尽管阿昔洛韦（ACV）及其衍生物在治疗复发性溶解性感染方面非常有效，但耐药菌株的出现仍然令人担忧。在这项研究中，评估了从古巴搁浅的棕色海藻马尾藻中获得的水醇提取物的体外抗疱疹活性。水醇提取物在 Vero 细胞中没有细胞毒性 (CC ₅₀ >5000 µg mL ^-1 )，并抑制 HSV-1（ACV 敏感和耐药）和 HSV-2（ACV 耐药）菌株的复制，EC ₅₀为 271.66，分别为403.62 和 14.99 µg mL ^-1。此外，关于作用机制的初步研究是用 ACV 敏感的 HSV-1 模型进行评估的。当与病毒预孵育以及将提取物和病毒同时添加到细胞上时，提取物表现出强烈的抑制作用。在感染后检测过程中，Vero 细胞的保护在长达 1 小时内非常有效。高分辨率 UPLC/MS-MS 分析检测到 139 种化合物，其中 44 种得到鉴定。进行计算机分析以确定提取物中鉴定出的两种目标黄酮与病毒糖蛋白 D (gD) 的假定相互作用位点。分子对接分析显示，takakin和鸢尾皂苷元主要通过疏水相互作用（Leu44、Pro50、Thr174、Lys169、Tyr208、Gln209）与gD蛋白活性中心相互作用，而氢键相互作用较少（Ser43、Asp46、Lys169、Tyr208）。这项研究对在海藻反复搁浅的情况下将S. Fluitans作为抗疱疹化合物来源的价值做出了贡献。