文献类型：期刊文献

英文题名：Discovery of potential small molecular SARS-CoV-2 entry blockers targeting the spike protein

作者：Wang, Lin[1,2];Wu, Yan[3];Yao, Sheng[4,5];Ge, Huan[6];Zhu, Ya[7];Chen, Kun[7];Chen, Wen-zhang[1];Zhang, Yi[1];Zhu, Wei[1];Wang, Hong-yang[2];Guo, Yu[8,9];Ma, Pei-xiang[1];Ren, Peng-xuan[1,2];Zhang, Xiang-lei[1,2];Li, Hui-qiong[1,2];Ali, Mohammad A.[10];Xu, Wen-qing[2];Jiang, Hua-liang[1,7];Zhang, Lei-ke[3];Zhu, Li-li[2,6];Ye, Yang[4,5];Shang, Wei-juan[3];Bai, Fang[1,2]

机构：[1]ShanghaiTech Univ, Shanghai Inst Adv Immunochem Studies, Shanghai 201210, Peoples R China;[2]ShanghaiTech Univ, Sch Life Sci & Technol, Shanghai 201210, Peoples R China;[3]Chinese Acad Sci, Wuhan Inst Virol, Ctr Biosafety Mega Sci, State Key Lab Virol, Wuhan 430064, Peoples R China;[4]Chinese Acad Sci, Shanghai Inst Mat Med, Dept Nat Prod Chem, Shanghai 201203, Peoples R China;[5]Chinese Acad Sci, Shanghai Inst Mat Med, State Key Lab Drug Res, Shanghai 201203, Peoples R China;[6]East China Univ Sci & Technol, Shanghai Key Lab New Drug Design, Sch Pharm, State Key Lab Bioreactor Engn, Shanghai 200237, Peoples R China;[7]Chinese Acad Sci, Shanghai Inst Mat Med, CAS Key Lab Receptor Res, Shanghai 201203, Peoples R China;[8]Nankai Univ, Coll Pharm, Tianjin 300071, Peoples R China;[9]Nankai Univ, State Key Lab Med Chem Biol, Tianjin 300071, Peoples R China;[10]King Saud Univ, Dept Bot & Microbiol, Coll Sci, Riyadh, Saudi Arabia

年份：2022

卷号：43

期号：4

起止页码：788

外文期刊名：ACTA PHARMACOLOGICA SINICA

收录：;WOS:【SCI-EXPANDED(收录号:WOS:000681173100002)】；

基金：We greatly thank Dr. Guo from Nan Kai University and the National Protein Center of China for providing protein samples. This work was supported by the Science and Technology Commission of Shanghai Municipality grants (Grant IDs: 20431900102, 20431900100, 20430780300, 21920102003 and 2043190012); the National Science and Technology Major Project "Key New Drug Creation and Manufacturing Program", China (Grant ID: 2018ZX09711002); National Natural Science Foundation of China (No. 21920102003); Shanghai Science and Technology Development Funds (Grant ID: 20QA1406400); the Youth Innovation Promotion Association CAS (grants 2018367 to LKZ); as well as the startup package from ShanghaiTech University.

语种：英文

外文关键词：SARS-CoV-2; natural products; virtual screening; spike protein; protein-protein interaction modulators

摘要：An epidemic of pneumonia caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is spreading worldwide. SARS-CoV-2 relies on its spike protein to invade host cells by interacting with the human receptor protein Angiotensin-Converting Enzymes 2 (ACE2). Therefore, designing an antibody or small-molecular entry blockers is of great significance for virus prevention and treatment. This study identified five potential small molecular anti-virus blockers via targeting SARS-CoV-2 spike protein by combining in silico technologies with in vitro experimental methods. The five molecules were natural products that binding to the RBD domain of SARS-CoV-2 was qualitatively and quantitively validated by both native Mass Spectrometry (MS) and Surface Plasmon Resonance (SPR). Anti-viral activity assays showed that the optimal molecule, H69C2, had a strong binding affinity (dissociation constant K-D) of 0.0947 mu M and anti-virus IC50 of 85.75 mu M.