Journal Article

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

Guo, Li, Li, Pei, Xiang, Zichun, Qian, Zhaohui, Ren, Lili, Hu, Keping, Chen, Xing, Jin, Qi, Mi, Dan, Mu, Zhixia, Guo, Ruixuan, Wang, Jianwei, Liu, Yan, Ou, Xiuyuan, Chen, Ting, Hu, Jiaxin, Chen, Jieyong, Lei, Xiaobo

2020

Overview

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. SARS-CoV-2 has spread globally. Here, the authors characterize the entry pathway of SARS-CoV-2, show that the SARS-CoV-2 spike protein is less stable than that of SARS-CoV, and show limited cross-neutralization activities between SARS-CoV and SARS-CoV-2 sera.

• Publisher: Nature Publishing Group UK,Nature Publishing Group,Nature Portfolio
• Subject: 13/1 / 13/106 / 13/109 / 13/31 / 14/63 / 38 / 38/22 / 38/23 / 42/70 / 631/250/2152/2153/1291 / 631/326/596/2078 / 631/326/596/2557 / 692/699/255/2514 / 82/83 / ACE2 / Angiotensin / Angiotensin-Converting Enzyme 2 / Antibodies / Antibodies, Viral - immunology / Betacoronavirus - chemistry / Betacoronavirus - immunology / Betacoronavirus - physiology / Broadly Neutralizing Antibodies - immunology / Calcium Channels - metabolism / Cathepsin L / Cathepsin L - metabolism / Cathepsins - antagonists & inhibitors / Cathepsins - metabolism / Cell Fusion / Coronaviridae / Coronavirus Infections - immunology / Coronaviruses / COVID-19 / Cross Reactions / Cross-reactivity / Drug development / Endocytosis / Giant Cells - physiology / Glycoproteins / HEK293 Cells / Humanities and Social Sciences / Humans / Immunosuppressive agents / multidisciplinary / Neutralization / Neutralization Tests / Pandemics / Peptidyl-dipeptidase A / Peptidyl-Dipeptidase A - metabolism / Phosphatidylinositol 3-Kinases - metabolism / Pneumonia, Viral - immunology / Protein Domains / Protein Multimerization / Proteins / Receptors, Virus - metabolism / SARS Virus - immunology / SARS-CoV-2 / Science / Science (multidisciplinary) / Severe Acute Respiratory Syndrome - immunology / Severe acute respiratory syndrome coronavirus 2 / Spike glycoprotein / Spike Glycoprotein, Coronavirus - chemistry / Spike Glycoprotein, Coronavirus - immunology / Spike Glycoprotein, Coronavirus - metabolism / Spike protein / Trypsin - metabolism / Vaccines / Viral diseases / Virus Internalization / Viruses