Characterization of spike glycoprotein of SARS-CoV-2 on virus entry and its immune cross-reactivity with SARS-CoV

被引:2283
作者
Ou, Xiuyuan [1 ]
Liu, Yan [1 ]
Lei, Xiaobo [1 ]
Li, Pei [1 ]
Mi, Dan [1 ]
Ren, Lili [1 ]
Guo, Li [1 ]
Guo, Ruixuan [1 ]
Chen, Ting [1 ]
Hu, Jiaxin [1 ]
Xiang, Zichun [1 ]
Mu, Zhixia [1 ]
Chen, Xing [2 ]
Chen, Jieyong [3 ]
Hu, Keping [2 ]
Jin, Qi [1 ]
Wang, Jianwei [1 ]
Qian, Zhaohui [1 ]
机构
[1] Chinese Acad Med Sci & Peking Union Med Coll, Inst Pathogen Biol, NHC Key Lab Syst Biol Pathogens, Beijing 100176, Peoples R China
[2] Chinese Acad Med Sci CAMS & Peking Union Med Coll, Inst Med Plant Dev IMPLAD, 151 Malianwa Rd North, Beijing 100193, Peoples R China
[3] Hengshui Third Peoples Hosp, Hebei, Peoples R China
基金
中国国家自然科学基金;
关键词
RESPIRATORY SYNDROME-CORONAVIRUS; RECEPTOR-BINDING DOMAIN; HOST-CELL ENTRY; EBOLA-VIRUS; MERS-COV; FUNCTIONAL RECEPTOR; PROTEIN; ACTIVATION; IDENTIFICATION; CLEAVAGE;
D O I
10.1038/s41467-020-15562-9
中图分类号
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号
07 ; 0710 ; 09 ;
摘要
Since 2002, beta coronaviruses (CoV) have caused three zoonotic outbreaks, SARS-CoV in 2002-2003, MERS-CoV in 2012, and the newly emerged SARS-CoV-2 in late 2019. However, little is currently known about the biology of SARS-CoV-2. Here, using SARS-CoV-2 S protein pseudovirus system, we confirm that human angiotensin converting enzyme 2 (hACE2) is the receptor for SARS-CoV-2, find that SARS-CoV-2 enters 293/hACE2 cells mainly through endocytosis, that PIKfyve, TPC2, and cathepsin L are critical for entry, and that SARS-CoV-2 S protein is less stable than SARS-CoV S. Polyclonal anti-SARS S1 antibodies T62 inhibit entry of SARS-CoV S but not SARS-CoV-2 S pseudovirions. Further studies using recovered SARS and COVID-19 patients' sera show limited cross-neutralization, suggesting that recovery from one infection might not protect against the other. Our results present potential targets for development of drugs and vaccines for SARS-CoV-2.
引用
收藏
页数:12
相关论文
共 53 条
[1]  
[Anonymous], VIRUS TAXONOMY 2018
[2]   Activation of the SARS coronavirus spike protein via sequential proteolytic cleavage at two distinct sites [J].
Belouzard, Sandrine ;
Chu, Victor C. ;
Whittaker, Gary R. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2009, 106 (14) :5871-5876
[3]   TMPRSS2 Activates the Human Coronavirus 229E for Cathepsin-Independent Host Cell Entry and Is Expressed in Viral Target Cells in the Respiratory Epithelium [J].
Bertram, Stephanie ;
Dijkman, Ronald ;
Habjan, Matthias ;
Heurich, Adeline ;
Gierer, Stefanie ;
Glowacka, Ilona ;
Welsch, Kathrin ;
Winkler, Michael ;
Schneider, Heike ;
Hofmann-Winkler, Heike ;
Thiel, Volker ;
Poehlmann, Stefan .
JOURNAL OF VIROLOGY, 2013, 87 (11) :6150-6160
[4]   Cleavage and Activation of the Severe Acute Respiratory Syndrome Coronavirus Spike Protein by Human Airway Trypsin-Like Protease [J].
Bertram, Stephanie ;
Glowacka, Ilona ;
Mueller, Marcel A. ;
Lavender, Hayley ;
Gnirss, Kerstin ;
Nehlmeier, Inga ;
Niemeyer, Daniela ;
He, Yuxian ;
Simmons, Graham ;
Drosten, Christian ;
Soilleux, Elizabeth J. ;
Jahn, Olaf ;
Steffen, Imke ;
Poehlmann, Stefan .
JOURNAL OF VIROLOGY, 2011, 85 (24) :13363-13372
[5]   PIKfyve Regulation of Endosome-Linked Pathways [J].
de Lartigue, Jane ;
Polson, Hannah ;
Feldman, Morri ;
Shokat, Kevan ;
Tooze, Sharon A. ;
Urbe, Sylvie ;
Clague, Michael J. .
TRAFFIC, 2009, 10 (07) :883-893
[6]   Ebola Virus Glycoprotein with Increased Infectivity Dominated the 2013-2016 Epidemic [J].
Diehl, William E. ;
Lin, Aaron E. ;
Grubaugh, Nathan D. ;
Carvalho, Luiz Max ;
Kim, Kyusik ;
Kyawe, Pyae Phyo ;
McCauley, Sean M. ;
Donnard, Elisa ;
Kucukural, Alper ;
McDonel, Patrick ;
Schaffner, Stephen F. ;
Garber, Manuel ;
Rambaut, Andrew ;
Andersen, Kristian G. ;
Sabeti, Pardis C. ;
Luban, Jeremy .
CELL, 2016, 167 (04) :1088-+
[7]   Identification of a novel coronavirus in patients with severe acute respiratory syndrome [J].
Drosten, C ;
Günther, S ;
Preiser, W ;
van der Werf, S ;
Brodt, HR ;
Becker, S ;
Rabenau, H ;
Panning, M ;
Kolesnikova, L ;
Fouchier, RAM ;
Berger, A ;
Burguière, AM ;
Cinatl, J ;
Eickmann, M ;
Escriou, N ;
Grywna, K ;
Kramme, S ;
Manuguerra, JC ;
Müller, S ;
Rickerts, V ;
Stürmer, M ;
Vieth, S ;
Klenk, HD ;
Osterhaus, ADME ;
Schmitz, H ;
Doerr, HW .
NEW ENGLAND JOURNAL OF MEDICINE, 2003, 348 (20) :1967-1976
[8]   The Spike Protein of the Emerging Betacoronavirus EMC Uses a Novel Coronavirus Receptor for Entry, Can Be Activated by TMPRSS2, and Is Targeted by Neutralizing Antibodies [J].
Gierer, Stefanie ;
Bertram, Stephanie ;
Kaup, Franziska ;
Wrensch, Florian ;
Heurich, Adeline ;
Kraemer-Kuehl, Annika ;
Welsch, Kathrin ;
Winkler, Michael ;
Meyer, Benjamin ;
Drosten, Christian ;
Dittmer, Ulf ;
von Hahn, Thomas ;
Simmons, Graham ;
Hofmann, Heike ;
Poehlmann, Stefan .
JOURNAL OF VIROLOGY, 2013, 87 (10) :5502-5511
[9]   Evidence that TMPRSS2 Activates the Severe Acute Respiratory Syndrome Coronavirus Spike Protein for Membrane Fusion and Reduces Viral Control by the Humoral Immune Response [J].
Glowacka, Ilona ;
Bertram, Stephanie ;
Mueller, Marcel A. ;
Allen, Paul ;
Soilleux, Elizabeth ;
Pfefferle, Susanne ;
Steffen, Imke ;
Tsegaye, Theodros Solomon ;
He, Yuxian ;
Gnirss, Kerstin ;
Niemeyer, Daniela ;
Schneider, Heike ;
Drosten, Christian ;
Poehlmann, Stefan .
JOURNAL OF VIROLOGY, 2011, 85 (09) :4122-4134
[10]   Isolation and characterization of viruses related to the SARS coronavirus from animals in Southern China [J].
Guan, Y ;
Zheng, BJ ;
He, YQ ;
Liu, XL ;
Zhuang, ZX ;
Cheung, CL ;
Luo, SW ;
Li, PH ;
Zhang, LJ ;
Guan, YJ ;
Butt, KM ;
Wong, KL ;
Chan, KW ;
Lim, W ;
Shortridge, KF ;
Yuen, KY ;
Peiris, JSM ;
Poon, LLM .
SCIENCE, 2003, 302 (5643) :276-278