Discovery of potential small molecular SARS-CoV-2 entry blockers targeting the spike protein

被引：49

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

来源：

ACTA PHARMACOLOGICA SINICA | 2022年 / 43卷 / 04期

基金：

上海市科技启明星计划; 中国国家自然科学基金;

关键词：

SARS-CoV-2; natural products; virtual screening; spike protein; protein-protein interaction modulators; INHIBITORS; BINDING; DOCKING; ACE2;

D O I：

10.1038/s41401-021-00735-z

中图分类号：

O6 [化学];

学科分类号：

0703 ;

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.

引用

页码：788 / 796

页数：9

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