Abstract

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.

中文翻译：

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免疫脂质体作为一种有前途的抗 SARS-CoV-2 抗病毒剂

摘要

据世界卫生组织称，截至2020年1月3日至2023年9月13日，俄罗斯联邦报告了约2300万例COVID-19确诊病例，其中约40万例死亡。考虑到含RNA病毒基因组的高突变率，不可避免地导致新的感染株（Eris和Pyrola）的出现，寻找药物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主动突变，这项任务需要全新的解决方案。这项研究提出了一种候选免疫脂质体药物，通过单克隆中和抗体 P4A1 靶向 SARS-CoV-2 的 S 蛋白，并确保高活性核糖核酸酶渗透到病毒感染的细胞中，从而降解细胞 RNA 和病毒 RNA 。我们证明，与游离单克隆中和抗体相比，所开发药物的中和活性增加了 40 倍以上。