The genus Orthobunyavirus are a group of viruses within arbovirus, with a zoonotic cycle, some of which could lead to human infection. A characteristic of these viruses is their lack of antiviral treatment or vaccine for its prevention. The objective of this work was to study the in vitro antiviral activity of nordihydroguaiaretic acid (NDGA), the most important active compound of Larrea divaricata Cav. (Zigophyllaceae), against Fort Sherman-like virus (FSV-like) as a model of Orthobunyavirus genus. At the same time, the effect of NDGA as a lipolytic agent on the cell cycle of this viral model was assessed. The method of reducing plaque forming units on LLC-MK2 cells was used to detect the action of NDGA on CbaAr426 and SFCrEq231 isolates of FSV-like. NDGA did not show virucidal effect, but it had antiviral activity with a similar inhibition in both isolates, which was dose dependent. It was established that the NDGA has a better inhibition one-hour post infection (p.i.), showing a different behavior in each isolate, which was dependent upon the time p.i. Since virus multiplication is dependent on host cell lipid metabolism, the antiviral effect of NDGA has been previously related to its ability to disturb the lipid metabolism, probably by interfering with the sterol regulatory element-binding proteins (SREBP) pathway and the 5-lipoxigenase (5-LOX). We determined by using caffeic acid, a 5-LOX inhibitor, that the inhibition of this enzyme negatively affected the FSV-like replication; and by the use of resveratrol, a SREBP1 inhibitor, it was showed that the negative regulation of this pathway only had action on the SFCrEq231 reduction. In addition, it was proved that the NDGA acts intracellularly, since it showed the ability to incorporate into LLC-MK2 cells. The information provided in this work converts the NDGA in a good antiviral candidate, especially for Orthobunyavirus infections, and a useful tool for the biochemical study of FSV-like that causes an infection poorly studied and potentially dangerous.

中文翻译：

---

关于去甲二氢愈创木酸对Fort Sherman样病毒（Orthobunyavirus）的抗病毒活性的首次报道

正畸病毒属是虫媒病毒中的一组病毒，具有人畜共患病周期，其中一些可能导致人类感染。这些病毒的特点是缺乏抗病毒治疗或疫苗预防。这项工作的目的是研究去甲二氢愈创木酸（NDGA）的体外抗病毒活性，去甲二氢愈创木酸是Larrea divaricata Cav的最重要活性化合物。（Zi科），作为Fort Sherman样病毒（FSV-like）的一种，作为Orbunbunyavirus属的模型。同时，评估了NDGA作为脂解剂对该病毒模型细胞周期的影响。使用减少LLC-MK2细胞上的噬斑形成单位的方法来检测NDGA对FSV样的CbaAr426和SFCrEq231分离株的作用。NDGA没有显示杀病毒作用，但在两种分离物中都具有抗病毒活性和相似的抑制作用，这是剂量依赖性的。已确定NDGA在感染后一小时（pi）具有更好的抑制作用，在每种分离株中表现出不同的行为，这取决于pi的时间。由于病毒的繁殖取决于宿主细胞脂质代谢，因此NDGA的抗病毒作用以前与它破坏脂质代谢的能力有关，可能是通过干扰固醇调节元件结合蛋白（SREBP）途径和5-脂氧合酶（5-LOX）引起的。我们通过使用5-LOX抑制剂咖啡酸来确定，对该酶的抑制会对FSV样复制产生负面影响。并且通过使用白藜芦醇（一种SREBP1抑制剂），表明该途径的负调控仅对SFCrEq231的减少有作用。另外，由于NDGA显示出掺入LLC-MK2细胞的能力，因此证明了NDGA在细胞内起作用。这项工作中提供的信息将NDGA转换为良好的抗病毒候选物，尤其是对于正念珠菌病毒感染，以及将其作为FSV样生化研究的有用工具，该研究导致对FSV的感染研究不充分且可能具有危险。