Development of a novel peptide to prevent entry of SARS-CoV-2 into lung and olfactory bulb cells of hACE2 expressing mice

被引：4

作者：

Su, Ping ^{[1
]}

Zhai, Dongxu ^{[1
]}

Wong, Albert H. C. ^{[1
,2
,4
,5
]}

Liu, Fang ^{[1
,2
,3
,4
]}

机构：

[1] Ctr Addict & Mental Hlth, Campbell Family Mental Hlth Res Inst, 250 Coll St, Toronto, ON M5T 1R8, Canada

[2] Univ Toronto, Dept Psychiat, Toronto, ON M5T 1R8, Canada

[3] Univ Toronto, Dept Physiol, Toronto, ON M5S 1A8, Canada

[4] Univ Toronto, Inst Med Sci, Toronto, ON M5S 1A8, Canada

[5] Univ Toronto, Fac Med, Dept Pharmacol, Toronto, ON M5S 1A8, Canada

来源：

MOLECULAR BRAIN | 2022年 / 15卷 / 01期

关键词：

Angiotensin-converting enzyme 2 (ACE2); COVID-19; Interfering peptide; SARS-CoV-2; Viral entry; RECEPTOR COMPLEX; NMDA RECEPTOR; SPIKE PROTEIN; INFECTION; TMPRSS2; INHIBITION; FUSION; GENE; ACE2;

D O I：

10.1186/s13041-022-00956-1

中图分类号：

Q189 [神经科学];

学科分类号：

071006 ;

摘要：

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a novel coronavirus that has caused a global pandemic Coronavirus Disease 2019 (COVID-19). Currently, there are no effective treatments specifically for COVID-19 infection. The initial step in SARS-CoV-2 infection is attachment to the angiotensin-converting enzyme 2 (ACE2) on the cell surface. We have developed a protein peptide that effectively disrupts the binding between the SARS-CoV-2 spike protein and ACE2. When delivered by nasal spray, our peptide prevents SARS-CoV-2 spike protein from entering lung and olfactory bulb cells of mice expressing human ACE2. Our peptide represents a potential novel treatment and prophylaxis against COVID-19.

引用

页数：13

共 43 条

[1] Comparative Review of SARS-CoV-2, SARS-CoV, MERS-CoV, and Influenza A Respiratory Viruses [J].

Abdelrahman, Zeinab ;

Li, Mengyuan ;

Wang, Xiaosheng .

FRONTIERS IN IMMUNOLOGY, 2020, 11

[2] The pathogenicity of SARS-CoV-2 in hACE2 transgenic mice [J].

Bao, Linlin ;

Deng, Wei ;

Huang, Baoying ;

Gao, Hong ;

Liu, Jiangning ;

Ren, Lili ;

Wei, Qiang ;

Yu, Pin ;

Xu, Yanfeng ;

Qi, Feifei ;

Qu, Yajin ;

Li, Fengdi ;

Lv, Qi ;

Wang, Wenling ;

Xue, Jing ;

Gong, Shuran ;

Liu, Mingya ;

Wang, Guanpeng ;

Wang, Shunyi ;

Song, Zhiqi ;

Zhao, Linna ;

Liu, Peipei ;

Zhao, Li ;

Ye, Fei ;

Wang, Huijuan ;

Zhou, Weimin ;

Zhu, Na ;

Zhen, Wei ;

Yu, Haisheng ;

Zhang, Xiaojuan ;

Guo, Li ;

Chen, Lan ;

Wang, Conghui ;

Wang, Ying ;

Wang, Xinming ;

Xiao, Yan ;

Sun, Qiangming ;

Liu, Hongqi ;

Zhu, Fanli ;

Ma, Chunxia ;

Yan, Lingmei ;

Yang, Mengli ;

Han, Jun ;

Xu, Wenbo ;

Tan, Wenjie ;

Peng, Xiaozhong ;

Jin, Qi ;

Wu, Guizhen ;

Qin, Chuan .

NATURE, 2020, 583 (7818) :830-+

[3] TMPRSS2 and furin are both essential for proteolytic activation of SARS-CoV-2 in human airway cells [J].

Bestle, Dorothea ;

Heindl, Miriam Ruth ;

Limburg, Hannah ;

Thuy Van Lam Van ;

Pilgram, Oliver ;

Moulton, Hong ;

Stein, David A. ;

Hardes, Kornelia ;

Eickmann, Markus ;

Dolnik, Olga ;

Rohde, Cornelius ;

Klenk, Hans-Dieter ;

Garten, Wolfgang ;

Steinmetzer, Torsten ;

Boettcher-Friebertshaeuser, Eva .

LIFE SCIENCE ALLIANCE, 2020, 3 (09)

[4] Severe acute respiratory syndrome coroavirus (SARS-CoV) infection inhibition using spike protein heptad repeat-derived peptides [J].

Bosch, BJ ;

Martina, BEE ;

van der Zee, R ;

Lepault, J ;

Haijema, BJ ;

Versluis, C ;

Heck, AJR ;

de Groot, R ;

Osterhaus, ADME ;

Rottier, PJM .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2004, 101 (22) :8455-8460

[5] Intranasal Delivery of a Peptide with Antidepressant-Like Effect [J].

Brown, Virginia ;

Liu, Fang .

NEUROPSYCHOPHARMACOLOGY, 2014, 39 (09) :2131-2141

[6] Establishment of pseudovirus infection mouse models for in vivo pharmacodynamics evaluation of filovirus entry inhibitors [J].

Chen, Qing ;

Tang, Ke ;

Zhang, Xiaoyu ;

Chen, Panpan ;

Guo, Ying .

ACTA PHARMACEUTICA SINICA B, 2018, 8 (02) :200-208

[7] How Viruses Invade Cells [J].

Cohen, Fredric S. .

BIOPHYSICAL JOURNAL, 2016, 110 (05) :1028-1032

[8] The spike glycoprotein of the new coronavirus 2019-nCoV contains a furinlike cleavage site absent in CoV of the same clade [J].

Coutard, B. ;

Valle, C. ;

de lamballerie, X. ;

Canard, B. ;

Seidah, N. G. ;

Decroly, E. .

ANTIVIRAL RESEARCH, 2020, 176

[9] Mechanisms of viral membrane fusion and its inhibition [J].

Eckert, DM ;

Kim, PS .

ANNUAL REVIEW OF BIOCHEMISTRY, 2001, 70 :777-810

[10] Survey of Human Chromosome 21 Gene Expression Effects on Early Development in Danio rerio [J].

Edie, Sarah ;

Zaghloul, Norann A. ;

Leitch, Carmen C. ;

Klinedinst, Donna K. ;

Lebron, Janette ;

Thole, Joey F. ;

McCallion, Andrew S. ;

Katsanis, Nicholas ;

Reeves, Roger H. .

G3-GENES GENOMES GENETICS, 2018, 8 (07) :2215-2223

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