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

  • Nat Commun. 2020 Mar 27;11(1):1620. doi: 10.1038/s41467-020-15562-9.
Xiuyuan Ou   #  1 ,  Yan Liu   #  1 ,  Xiaobo Lei   #  1 ,  Pei Li  1 ,  Dan Mi  1 ,  Lili Ren  1 ,  Li Guo  1 ,  Ruixuan Guo  1 ,  Ting Chen  1 ,  Jiaxin Hu  1 ,  Zichun Xiang  1 ,  Zhixia Mu  1 ,  Xing Chen  2 ,  Jieyong Chen  3 ,  Keping Hu  2 ,  Qi Jin  4 ,  Jianwei Wang  5 ,  Zhaohui Qian  6
Affiliations
  • 1. NHC Key laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 100176, Beijing, China.
  • 2. Institute of Medicinal Plant Development (IMPLAD), Chinese Academy of Medical Sciences (CAMS) and Peking Union Medical Collage (PUMC), 151 Malianwa Road North, Haidian District, 100193, Beijing, China.
  • 3. Hengshui Third People's Hospital, Heibei, China.
  • 4. NHC Key laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 100176, Beijing, China. [email protected].
  • 5. NHC Key laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 100176, Beijing, China. [email protected].
  • 6. NHC Key laboratory of Systems Biology of Pathogens, Institute of Pathogen Biology, Chinese Academy of Medical Sciences and Peking Union Medical College, 100176, Beijing, China. [email protected].
  • # Contributed equally.
PMID: 32221306 DOI: 10.1038/s41467-020-15562-9
Abstract

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.

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