Background: The severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) epidemic has resulted in thousands of infections and deaths worldwide. Several therapies are currently undergoing clinical trials for the treatment of SARS-CoV-2 infection. However, the development of new drugs and the repositioning of existing drugs can only be achieved after the identification of potential therapeutic targets within structures, as this strategy provides the most precise solution for developing treatments for sudden epidemic infectious diseases. Summary: In the current investigation, crystal and cryo-electron microscopy structures encoded by the SARS-CoV-2 genome were systematically examined for the identification of potential drug targets. These structures include nonstructural proteins (Nsp-9; Nsp-12; and Nsp-15), nucleocapsid (N) proteins, and the main protease (M^pro). Key Message: The structural information reveals the presence of many potential alternative therapeutic targets, primarily involved in interaction between N protein and Nsp3, forming replication-transcription complexes (RTCs) which might be a potential drug target for effective control of current SARS-CoV-2 pandemic. RTCs consist of 16 nonstructural proteins (Nsp1-16) that play the most essential role in the synthesis of viral RNA. Targeting the physical linkage between the envelope and single-stranded positive RNA, a process facilitated by matrix proteins may provide a good alternative strategy. Our current study provides useful information for the development of new lead compounds against SARS-CoV-2 infections.
Intervirology

中文翻译：

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SARS-CoV-2 RNA结合蛋白的结构和治疗靶标

背景：严重的急性呼吸系统综合症冠状病毒2（SARS-CoV-2）流行已导致全世界成千上万的感染和死亡。目前有几种疗法正在治疗SARS-CoV-2感染。但是，只有在确定结构内潜在的治疗靶点后，才能实现新药的开发和现有药物的重新定位，因为该策略为开发突发性传染病提供了最精确的解决方案。概要：在当前的研究中，系统地检查了SARS-CoV-2基因组编码的晶体和低温电子显微镜结构，以确定潜在的药物靶标。这些结构包括非结构蛋白（Nsp-9，Nsp-12和Nsp-15），核衣壳（N）蛋白和主要蛋白酶（M ^pro）。关键信息：结构信息揭示了许多潜在的替代治疗靶标的存在，这些靶标主要参与N蛋白和Nsp3之间的相互作用，形成复制-转录复合物（RTC），可能是有效控制当前SARS-CoV-2大流行的潜在药物靶标。RTC由16个非结构蛋白（Nsp1-16）组成，这些蛋白在病毒RNA的合成中起最重要的作用。靶向包膜和单链阳性RNA之间的物理连接，基质蛋白促进的过程可能提供了很好的替代策略。我们当前的研究为开发抗SARS-CoV-2感染的新型先导化合物提供了有用的信息。
病毒学