G.P. Somov Institute of Epidemiology and Microbiology, Rospotrebnadzor, 690087 Vladivostok, Russia.
G.B. Elyakov Pacific Institute of Bioorganic Chemistry, Far-Eastern Branch of the Russian Academy of Sciences, 690022 Vladivostok, Russia.
Int J Mol Sci. 2022 Dec 12;23(24):15754. doi: 10.3390/ijms232415754.
Herpes simplex virus (HSV) infections, the incidence of which is still widespread throughout the world, are actualizing the search and development of new, more effective antiherpetic drugs. The development of multifunctional drug delivery systems, including liposome-based ones, has become a relevant and attractive concept in nanotechnology. The ability of complexes of κ- and Σ-carrageenans (CRGs)-sulfated polysaccharides of red algae, with echinochrome A (Ech), as well as the liposomal form of the Σ-CRG/Ech complex-to inhibit different stages of HSV-1 infection in Vero cells was studied. By quantum chemical calculations, it was shown that CRG forms stable complexes with Ech. We have shown that complexes of κ-CRG/Ech and Σ-CRG/Ech exhibit highest virucidal activity with a selectivity index (SI) of 270 and 350, respectively, and inhibition of virus-cell interaction (SI of 83 and 32, respectively). The liposomal form of the Σ-CRG/Ech complex after virus adsorption and penetration to cells effectively reduced the HSV-1 plaque formation. The virus-inhibiting activity of the liposomal form of the Σ-CRG/Ech complex was three times higher than that of the Σ-CRG/Ech complex itself. Obtaining CRGs/Ech complexes and their liposomal forms can become the basis of a successful strategy for the development of promising antiherpetic drugs.
单纯疱疹病毒(HSV)感染在全球范围内仍广泛存在,这促使人们对新型、更有效的抗疱疹药物进行研究和开发。多功能药物递送系统的发展,包括基于脂质体的系统,已成为纳米技术中一个相关且有吸引力的概念。卡拉胶(κ-和 Σ-)-硫酸化多糖与海胆酮 A(Ech)复合物以及 Σ-CRG/Ech 脂质体复合物抑制 Vero 细胞中 HSV-1 感染不同阶段的能力的研究。通过量子化学计算表明,CRG 与 Ech 形成稳定的复合物。我们已经表明,κ-CRG/Ech 和 Σ-CRG/Ech 复合物具有最高的病毒杀灭活性,选择性指数(SI)分别为 270 和 350,并且抑制病毒-细胞相互作用(SI 分别为 83 和 32)。在病毒吸附和穿透细胞后,Σ-CRG/Ech 脂质体复合物有效降低了 HSV-1 斑块的形成。Σ-CRG/Ech 脂质体复合物的病毒抑制活性比 Σ-CRG/Ech 复合物本身高 3 倍。获得 CRGs/Ech 复合物及其脂质体形式可能成为开发有前途的抗疱疹药物的成功策略的基础。