G.P. Somov Institute of Epidemiology and Microbiology, Rospotrebnadzor, Selskaya Street, 1, 690087 Vladivostok, Russia.
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Science, Prospect 100 let Vladivostoku, 159, 690022 Vladivostok, Russia.
Mar Drugs. 2021 Oct 15;19(10):577. doi: 10.3390/md19100577.
The Hantaan orthohantavirus (genovariant Amur-AMRV) is a rodent-borne zoonotic virus; it is the causative agent of haemorrhagic fever with renal syndrome in humans. The currently limited therapeutic options require the development of effective anti-orthohantavirus drugs. The ability of native fucoidan from (FeF) and its enzymatically prepared high-molecular-weight (FeHMP) and low-molecular-weight (FeLMP) fractions to inhibit different stages of AMRV infection in Vero cells was studied. The structures of derivatives obtained were determined using nuclear magnetic resonance (NMR) spectroscopy. We found that fucoidan and its derivatives exhibited significant antiviral activity by affecting the early stages of the AMRV lifecycle, notably virus attachment and penetration. The FeHMP and FeLMP fractions showed the highest anti-adsorption activity by inhibiting AMRV focus formation, with a selective index (SI) > 110; FeF had an SI of ~70. The FeLMP fraction showed a greater virucidal effect compared with FeF and the FeHMP fraction. It was shown by molecular docking that 2-sulphated fucotetrasaccharide, a main component of the FeLMP fraction, is able to bind with the AMRV envelope glycoproteins Gn/Gc and with integrin β3 to prevent virus-cell interactions. The relatively small size of these sites of interactions explains the higher anti-AMRV activity of the FeLMP fraction.
汉坦病毒（阿穆尔-AMRV 基因变体）是一种啮齿动物传播的人畜共患病病毒；它是人类肾综合征出血热的病原体。目前有限的治疗选择需要开发有效的抗正粘病毒药物。本研究旨在探讨天然褐藻糖胶（FeF）及其酶解得到的高分子量（FeHMP）和低分子量（FeLMP）部分对 AMRV 在 Vero 细胞中不同感染阶段的抑制作用。利用核磁共振（NMR）光谱确定了衍生物的结构。研究发现，褐藻糖胶及其衍生物通过影响 AMRV 生命周期的早期阶段，特别是病毒附着和渗透，表现出显著的抗病毒活性。FeHMP 和 FeLMP 部分通过抑制 AMRV 焦点形成表现出最高的抗吸附活性，选择性指数（SI）>110；FeF 的 SI 约为 70。与 FeF 和 FeHMP 部分相比，FeLMP 部分显示出更强的病毒杀灭作用。分子对接表明，FeLMP 部分的主要成分 2-硫酸化岩藻四糖能够与 AMRV 包膜糖蛋白 Gn/Gc 和整合素β3结合，从而阻止病毒与细胞的相互作用。这些相互作用位点的相对较小尺寸解释了 FeLMP 部分具有更高的抗 AMRV 活性。
