Advances in Magnetic Microbead Affinity Selection Screening: Discovery of Natural Ligands to the SARS-CoV-2 Spike Protein.
Advances in Magnetic Microbead Affinity Selection Screening: Discovery of Natural Ligands to the SARS-CoV-2 Spike Protein.
复制标题
DOI：
10.1021/jasms.1c00318
复制
发表时间：
2022-01-05
影响因子：
3.2
通讯作者：
van Breemen, Richard B.
中科院分区：
文献类型：
--
作者：
Muchiri, Ruth N.;Kibitel, James;Redick, Margaret A.;van Breemen, Richard B.
亲和选择-质谱法，包括磁性微珠亲和选择-筛选（MagMASS），是在复杂混合物中发现与药理学靶点结合的配体的理想方法。需要治疗剂来预防或治疗由严重急性呼吸道综合征冠状病毒2（SARS-CoV-2）引起的COVID-19。SARS-CoV-2感染人类细胞涉及病毒刺突蛋白亚基1（S1）与人类细胞受体血管紧张素转换酶-2（ACE 2）的结合。与抗体一样，小分子具有阻断病毒S1蛋白与人ACE 2相互作用并预防SARS-CoV-2感染的潜力。因此，开发了MagMASS测定用于发现S1蛋白的配体。与以前的MagMASS方法不同，这种新的检测方法使用机器人技术，将通量和灵敏度提高了五倍。使用SBP-1肽，这是相同的ACE 2的氨基酸序列识别的S1蛋白，然后应用于从植物提取物中发现的天然配体的测定进行了验证。S1蛋白的小分子配体在甘草种的提取物中被发现。特别是，甘草配体甘草查尔酮A，确定通过复制和比较标准使用高效液相色谱与高分辨率串联质谱。开发了一种使用磁性微珠亲和选择筛选（MagMASS）的基于质谱的检测方法，以促进发现导致COVID-19的SARS-CoV-2刺突蛋白的配体。通过应用MagMASS筛选植物提取物，甘草查尔酮A从甘草被确定为S1刺突蛋白的配体。病毒刺突蛋白的配体具有阻断病毒与人细胞受体ACE 2结合并抑制感染的潜力。
Affinity selection-mass spectrometry, which includes magnetic microbead affinity selection-screening (MagMASS), is ideal for the discovery of ligands in complex mixtures that bind to pharmacological targets. Therapeutic agents are needed to prevent or treat COVID-19, which is caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Infection of human cells by SARS-CoV-2 involves binding of the virus spike protein subunit 1 (S1) to the human cell receptor angiotensin converting enzyme-2 (ACE2). Like antibodies, small molecules have the potential to block the interaction of the viral S1 protein with human ACE2 and prevent SARS-CoV-2 infection. Therefore, a MagMASS assay was developed for the discovery of ligands to the S1 protein. Unlike previous MagMASS approaches, this new assay used robotics for five-fold enhancement of throughput and sensitivity. The assay was validated using the SBP-1 peptide, which is identical to the ACE2 amino acid sequence recognized by the S1 protein, and then applied to the discovery of natural ligands from botanical extracts. Small molecule ligands to the S1 protein were discovered in extracts of the licorice species, Glycyrrhiza inflata. In particular, the licorice ligand licochalcone A was identified through dereplication and comparison with standards using HPLC with high-resolution tandem mass spectrometry. A mass spectrometry-based assay using magnetic microbead affinity-selection screening (MagMASS) was developed to facilitate the discovery of ligands to the spike protein of SARS-CoV-2, which causes COVID-19. By applying MagMASS to the screening of botanical extracts, licochalcone A from licorice was identified as a ligand to the S1 spike protein. Ligands to the virus spike protein have the potential to block virus binding to the human cell receptor ACE2 and inhibit infection.
登录
查看更多内容
影响因子：
18.2
作者：
Pomplun S;Jbara M;Quartararo AJ;Zhang G;Brown JS;Lee YC;Ye X;Hanna S;Pentelute BL
通讯作者：
Pentelute BL
BSA 功能化 Fe3O4 磁性纳米颗粒与 HPLC-MS/MS 联用筛选和鉴定葛花中 BSA 结合配体
DOI：
10.1016/j.jchromb.2012.01.008
发表时间：
2012-03-01
影响因子：
3
作者：
Liu, Liangliang;Ma, Yongjian;Shi, Shuyun
通讯作者：
Shi, Shuyun
影响因子：
7.4
作者：
vanBreemen, RB;Huang, CR;Venton, DL
通讯作者：
Venton, DL
影响因子：
7.4
作者：
Liu, Dongting;Guo, Jian;van Breemen, Richard B.
通讯作者：
van Breemen, Richard B.
影响因子：
7.3
作者：
Zhao, YZ;vanBreemen, RB;Venton, DL
通讯作者：
Venton, DL