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

2020/03/27 by Xiuyuan Ou, Yan Liu, Xiaobo Lei +15 · 9 citations
Medicine · #COVID-19 Clinical Research Studies #SARS-CoV-2 and COVID-19 Research #Viral Infections and Outbreaks Research

paper · pdf · doi:10.1038/s41467-020-15562-9

openalex publication_date 2020/03/27 · openalex created_date 2025/10/10 · openalex updated_date 2026/07/25

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.

Citations

• Clinical features of patients infected with 2019 novel coronavirus in Wuhan, China
• A Novel Coronavirus from Patients with Pneumonia in China, 2019
• A pneumonia outbreak associated with a new coronavirus of probable bat origin
• SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

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• Design, Synthesis, and Unprecedented Interactions of Covalent Dipeptide-Based Inhibitors of SARS-CoV-2 Main Protease and Its Variants Displaying Potent Antiviral Activity
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