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

被引：48

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：

中国国家自然科学基金; 上海市科技启明星计划;

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

共 50 条

[41] Simulations of the spike: molecular dynamics and SARS-CoV-2
Conrado Pedebos
Syma Khalid
Nature Reviews Microbiology, 2022, 20 : 192 - 192
[42] Targeting novel coronavirus SARS-CoV-2 spike protein with phytoconstituents of Momordica charantia
Santosh Kumar Singh
Shailesh Singh
Rajesh Singh
Journal of Ovarian Research, 14
[43] In silico targeting SARS-CoV-2 spike protein and main protease by biochemical compounds
Laleh Babaeekhou
Maryam Ghane
Mahdi Abbas-Mohammadi
Biologia, 2021, 76 : 3547 - 3565
[44] Recombinant protein targeting and opsonizing spike glycoprotein for enhancing SARS-CoV-2 phagocytosis
Khattabi, Latifa
MEDICAL HYPOTHESES, 2020, 143
[45] Targeting novel coronavirus SARS-CoV-2 spike protein with phytoconstituents of Momordica charantia
Singh, Santosh Kumar
Singh, Shailesh
Singh, Rajesh
JOURNAL OF OVARIAN RESEARCH, 2021, 14 (01)
[46] In silico targeting SARS-CoV-2 spike protein and main protease by biochemical compounds
Babaeekhou, Laleh
Ghane, Maryam
Abbas-Mohammadi, Mahdi
BIOLOGIA, 2021, 76 (11) : 3547 - 3565
[47] Cellular signalling by SARS-CoV-2 spike protein
Gracie, Nicholas P.
Lai, Lachlan Y. S.
Newsome, Timothy P.
MICROBIOLOGY AUSTRALIA, 2024, 45 (01) : 13 - 17
[48] Identification of potential SARS-CoV-2 entry inhibitors by targeting the interface region between the spike RBD and human ACE2
Gurung, Arun Bahadur
Ali, Mohammad Ajmal
Lee, Joongku
Abul Farah, Mohammad
Al-Anazi, Khalid Mashay
JOURNAL OF INFECTION AND PUBLIC HEALTH, 2021, 14 (02) : 227 - 237
[49] The Elusive Coreceptors for the SARS-CoV-2 Spike Protein
Berkowitz, Reed L. L.
Ostrov, David A. A.
VIRUSES-BASEL, 2023, 15 (01):
[50] SARS-CoV-2 Spike Protein Interaction Space
Lungu, Claudiu N.
Putz, Mihai V.
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2023, 24 (15)

← 1 2 3 4 5 →