Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, Russian Academy of Sciences, Moscow, Russia.
Moscow State University, Moscow, Russia.
Dokl Biochem Biophys. 2024 Feb;514(1):6-10. doi: 10.1134/S1607672923700618. Epub 2024 Jan 7.
According to the World Health Organization, as of January 3, 2020 to September 13, 2023, there were approximately 23 million confirmed cases of COVID-19 reported in the Russian Federation, about 400 thousand of which were fatal. Considering the high rate of mutation of the RNA-containing virus genome, which inevitably leads to the emergence of new infectious strains (Eris and Pyrola), the search for medicinal antiviral agents remains an urgent task. Moreover, taking into account the actively mutating receptor-binding domain, this task requires fundamentally new solutions. This study proposes a candidate immunoliposomal drug that targets the S protein of SARS-CoV-2 by the monoclonal neutralizing antibody P4A1 and ensures the penetration of a highly active ribonuclease into the virus-infected cell, which degrades, among cellular RNA, viral RNA too. We demonstrate a more than 40-fold increase in the neutralizing activity of the developed drug compared to the free monoclonal neutralizing antibody.
根据世界卫生组织的数据，截至 2020 年 1 月 3 日至 2023 年 9 月 13 日，俄罗斯联邦报告了大约 2300 万例 COVID-19 确诊病例，其中约 40 万人死亡。考虑到含有 RNA 的病毒基因组的高突变率，这不可避免地导致新的传染性菌株（Eris 和 Pyrola）的出现，寻找药用抗病毒药物仍然是一项紧迫的任务。此外，考虑到受体结合域的积极突变，这项任务需要全新的解决方案。本研究提出了一种候选免疫脂质体药物，该药物通过单克隆中和抗体 P4A1 靶向 SARS-CoV-2 的 S 蛋白，并确保高度活跃的核糖核酸酶进入病毒感染的细胞，该酶在细胞 RNA 中降解，包括病毒 RNA。我们证明，与游离的单克隆中和抗体相比，开发的药物的中和活性提高了 40 多倍。
