Coronavirus membrane fusion mechanism offers a potential target for antiviral development

被引:536
作者
Tang, Tiffany [1 ]
Bidon, Miya [1 ]
Jaimes, Javier A. [2 ]
Whittaker, Gary R. [2 ]
Daniel, Susan [1 ]
机构
[1] Cornell Univ, Robert Frederick Smith Sch Chem & Biomol Engn, Ithaca, NY 14853 USA
[2] Cornell Univ, Dept Microbiol & Immunol, Ithaca, NY 14853 USA
基金
美国国家科学基金会; 美国国家卫生研究院;
关键词
Middle east respiratory syndrome; Severe acute respiratory syndrome; SARS-CoV-2; COVID-19; Spike protein; Fusion peptide; RESPIRATORY SYNDROME-CORONAVIRUS; SARS-COV ENTRY; SPIKE PROTEIN; CELL ENTRY; MERS-COV; LIPID RAFTS; FUNCTIONAL RECEPTOR; CATHEPSIN-L; PROTEOLYTIC ACTIVATION; SERINE PROTEASES;
D O I
10.1016/j.antiviral.2020.104792
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
The coronavirus disease 2019 (COVID-19) pandemic has focused attention on the need to develop effective therapies against the causative agent, SARS-CoV-2, and also against other pathogenic coronaviruses (CoV) that have emerged in the past or might appear in future. Researchers are therefore focusing on steps in the CoV replication cycle that may be vulnerable to inhibition by broad-spectrum or specific antiviral agents. The conserved nature of the fusion domain and mechanism across the CoV family make it a valuable target to elucidate and develop pan-CoV therapeutics. In this article, we review the role of the CoV spike protein in mediating fusion of the viral and host cell membranes, summarizing the results of research on SARS-CoV, MERS-CoV, and recent peer-reviewed studies of SARS-CoV-2, and suggest that the fusion mechanism be investigated as a potential antiviral target. We also provide a supplemental file containing background information on the biology, epidemiology, and clinical features of all human-infecting coronaviruses, along with a phylogenetic tree of these coronaviruses.
引用
收藏
页数:16
相关论文
共 148 条
[1]   A Fusion Peptide in the Spike Protein of MERS Coronavirus [J].
Alsaadi, Entedar A. J. ;
Neuman, Benjamin W. ;
Jones, Ian M. .
VIRUSES-BASEL, 2019, 11 (09)
[2]   The proximal origin of SARS-CoV-2 [J].
Andersen, Kristian G. ;
Rambaut, Andrew ;
Lipkin, W. Ian ;
Holmes, Edward C. ;
Garry, Robert F. .
NATURE MEDICINE, 2020, 26 (04) :450-452
[3]  
[Anonymous], J MOLEC BIOL
[4]  
[Anonymous], PNAS
[5]  
[Anonymous], J VIROLOGY
[6]  
[Anonymous], CD26 MEDIATED SIGNAL
[7]  
[Anonymous], INTRANASALLY ADMINIS
[8]   Receptor Variation and Susceptibility to Middle East Respiratory Syndrome Coronavirus Infection [J].
Barlan, Arlene ;
Zhao, Jincun ;
Sarkar, Mayukh K. ;
Li, Kun ;
McCray, Paul B., Jr. ;
Perlman, Stanley ;
Gallagher, Tom .
JOURNAL OF VIROLOGY, 2014, 88 (09) :4953-4961
[9]   Mechanisms of Coronavirus Cell Entry Mediated by the Viral Spike Protein [J].
Belouzard, Sandrine ;
Millet, Jean K. ;
Licitra, Beth N. ;
Whittaker, Gary R. .
VIRUSES-BASEL, 2012, 4 (06) :1011-1033
[10]   Elastase-mediated Activation of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein at Discrete Sites within the S2 Domain [J].
Belouzard, Sandrine ;
Madu, Ikenna ;
Whittaker, Gary R. .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (30) :22756-22761