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.

引用

页码：788 / 796

页数：8

共 119 条

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