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
[11]   NAADP-dependent Ca2+ signaling regulates Middle East respiratory syndrome-coronavirus pseudovirus translocation through the endolysosomal system [J].
Gunaratne, Gihan S. ;
Yang, Yang ;
Li, Fang ;
Walseth, Timothy F. ;
Marchant, Jonathan S. .
CELL CALCIUM, 2018, 75 :30-41
[12]   Influence of glenohumeral joint muscle insertion on moment arms using a finite element model [J].
Hoffmann, M. ;
Begon, M. ;
Lafon, Y. ;
Duprey, S. .
COMPUTER METHODS IN BIOMECHANICS AND BIOMEDICAL ENGINEERING, 2020, 23 (14) :1117-1126
[13]  
Huang CL, 2020, LANCET, V395, P497, DOI [10.1016/S0140-6736(20)30183-5, 10.1016/S0140-6736(20)30211-7]
[14]   Human Coronavirus HKU1 Spike Protein Uses O-Acetylated Sialic Acid as an Attachment Receptor Determinant and Employs Hemagglutinin-Esterase Protein as a Receptor-Destroying Enzyme [J].
Huang, Xingchuan ;
Dong, Wenjuan ;
Milewska, Aleksandra ;
Golda, Anna ;
Qi, Yonghe ;
Zhu, Quan K. ;
Marasco, Wayne A. ;
Baric, Ralph S. ;
Sims, Amy C. ;
Pyrc, Krzysztof ;
Li, Wenhui ;
Sui, Jianhua .
JOURNAL OF VIROLOGY, 2015, 89 (14) :7202-7213
[15]   Human coronaviruses OC43 and HKU1 bind to 9-O-acetylated sialic acids via a conserved receptor-binding site in spike protein domain A [J].
Hulswit, Ruben J. G. ;
Lang, Yifei ;
Bakkers, Mark J. G. ;
Li, Wentao ;
Li, Zeshi ;
Schouten, Arie ;
Ophorst, Bram ;
van Kuppeveld, Frank J. M. ;
Boons, Geert-Jan ;
Bosch, Berend-Jan ;
Huizinga, Eric G. ;
de Groot, Raoul J. .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2019, 116 (07) :2681-2690
[16]  
Kamps BS, 2003, SARS REFERENCE
[17]   A novel coronavirus associated with severe acute respiratory syndrome [J].
Ksiazek, TG ;
Erdman, D ;
Goldsmith, CS ;
Zaki, SR ;
Peret, T ;
Emery, S ;
Tong, SX ;
Urbani, C ;
Comer, JA ;
Lim, W ;
Rollin, PE ;
Dowell, SF ;
Ling, AE ;
Humphrey, CD ;
Shieh, WJ ;
Guarner, J ;
Paddock, CD ;
Rota, P ;
Fields, B ;
DeRisi, J ;
Yang, JY ;
Cox, N ;
Hughes, JM ;
LeDuc, JW ;
Bellini, WJ ;
Anderson, LJ .
NEW ENGLAND JOURNAL OF MEDICINE, 2003, 348 (20) :1953-1966
[18]   LOCALIZATION OF NEUTRALIZING EPITOPES AND THE RECEPTOR-BINDING SITE WITHIN THE AMINO-TERMINAL 330 AMINO-ACIDS OF THE MURINE CORONAVIRUS SPIKE PROTEIN [J].
KUBO, H ;
YAMADA, YK ;
TAGUCHI, F .
JOURNAL OF VIROLOGY, 1994, 68 (09) :5403-5410
[19]   Structure of SARS coronavirus spike receptor-binding domain complexed with receptor [J].
Li, F ;
Li, WH ;
Farzan, M ;
Harrison, SC .
SCIENCE, 2005, 309 (5742) :1864-1868
[20]   Receptor Recognition Mechanisms of Coronaviruses: a Decade of Structural Studies [J].
Li, Fang .
JOURNAL OF VIROLOGY, 2015, 89 (04) :1954-1964