Small molecule therapeutic agents are needed to treat or prevent infections by severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), which is the cause of the COVID-19 pandemic. To expedite the discovery of lead compounds for development, assays have been developed based on affinity selection-mass spectrometry (AS-MS), which enables the rapid screening of mixtures such as combinatorial libraries and extracts of botanicals or other sources of natural products. AS-MS assays have been used to find ligands to the SARS-CoV-2 spike protein for inhibition of cell entry as well as to the 3-chymotrypsin-like cysteine protease (3CLpro) and the RNA-dependent RNA polymerase complex constituent Nsp9, which are targets for inhibition of viral replication. The AS-MS approach of magnetic microbead affinity selection screening has been used to discover high-affinity peptide ligands to the spike protein as well as the hemp cannabinoids cannabidiolic acid and cannabigerolic acid, which can prevent cell infection by SARS-CoV-2. Another AS-MS method, native mass spectrometry, has been used to discover that the flavonoids baicalein, scutellarein, and ganhuangenin, can inhibit the SARS-CoV-2 protease 3CLpro. Native mass spectrometry has also been used to find an ent-kaurane natural product, oridonin, that can bind to the viral protein Nsp9 and interfere with RNA replication. These natural lead compounds are under investigation for the development of therapeutic agents to prevent or treat SARS-CoV-2 infection.

中文翻译：

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亲和选择-质谱法在抗 SARS-CoV-2 化合物发现中的应用

需要小分子治疗药物来治疗或预防严重急性呼吸综合征冠状病毒-2 (SARS-CoV-2) 感染，该病毒是导致 COVID-19 大流行的原因。为了加快先导化合物的发现和开发，基于亲和选择质谱 (AS-MS) 开发了检测方法，能够快速筛选混合物，例如组合文库和植物提取物或其他天然产物来源。AS-MS 检测已用于寻找 SARS-CoV-2 刺突蛋白的配体，以抑制细胞进入，以及 3-胰凝乳蛋白酶样半胱氨酸蛋白酶 (3CLpro) 和 RNA 依赖性 RNA 聚合酶复合物成分 Nsp9 的配体，它们是抑制病毒复制的靶标。磁性微珠亲和力选择筛选的 AS-MS 方法已用于发现刺突蛋白以及大麻素大麻二酚酸和大麻二酚酸的高亲和力肽配体，它们可以预防 SARS-CoV-2 的细胞感染。另一种 AS-MS 方法，即天然质谱法，已被用于发现黄酮类化合物黄芩素、黄芩素和甘黄根素可以抑制 SARS-CoV-2 蛋白酶 3CLpro。天然质谱也已被用来寻找一种对映贝壳杉烷天然产物冬凌草甲素，它可以与病毒蛋白 Nsp9 结合并干扰 RNA 复制。正在研究这些天然先导化合物，以开发预防或治疗 SARS-CoV-2 感染的治疗剂。