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

被引:0
作者
Lin Wang
Yan Wu
Sheng Yao
Huan Ge
Ya Zhu
Kun Chen
Wen-zhang Chen
Yi Zhang
Wei Zhu
Hong-yang Wang
Yu Guo
Pei-xiang Ma
Peng-xuan Ren
Xiang-lei Zhang
Hui-qiong Li
Mohammad A. Ali
Wen-qing Xu
Hua-liang Jiang
Lei-ke Zhang
Li-li Zhu
Yang Ye
Wei-juan Shang
Fang Bai
机构
[1] ShanghaiTech University,Shanghai Institute for Advanced Immunochemical Studies
[2] ShanghaiTech University,School of Life Science and Technology
[3] Chinese Academy of Sciences,State Key Laboratory of Virology, Wuhan Institute of Virology, Center for Biosafety Mega
[4] Chinese Academy of Sciences,Science
[5] Chinese Academy of Sciences,Department of Natural Products Chemistry, Shanghai Institute of Materia Medica
[6] East China University of Science and Technology,State Key Laboratory of Drug Research, Shanghai Institute of Materia Medica
[7] Chinese Academy of Sciences,State Key Laboratory of Bioreactor Engineering, Shanghai Key Laboratory of New Drug Design, School of Pharmacy
[8] Nankai University,CAS Key Laboratory of Receptor Research, Shanghai Institute of Materia Medica
[9] King Saud University,College of Pharmacy and State Key Laboratory of Medicinal Chemical Biology
来源
Acta Pharmacologica Sinica | 2022年 / 43卷
关键词
SARS-CoV-2; natural products; virtual screening; spike protein; protein-protein interaction modulators;
D O I
暂无
中图分类号
学科分类号
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 KD) of 0.0947 µM and anti-virus IC50 of 85.75 µM.
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页码:788 / 796
页数:8
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