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

• Published in: Nature Communications Vol. 11; no. 1; p. 1620
• Main Authors: Ou, Xiuyuan, Liu, Yan, Lei, Xiaobo, Li, Pei, Mi, Dan, Ren, Lili, Guo, Li, Guo, Ruixuan, Chen, Ting, Hu, Jiaxin, Xiang, Zichun, Mu, Zhixia, Chen, Xing, Chen, Jieyong, Hu, Keping, Jin, Qi, Wang, Jianwei, Qian, Zhaohui
• Format: Journal Article Web Resource
• Language: English
• Published: London Nature Publishing Group UK 27.03.2020; Nature Publishing Group; Springer Nature B.V; Nature Portfolio
• Subjects: 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; 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
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-15562-9

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.