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

By Xiuyuan Ou, Yan Liu, X. Lei, Pei Li, Dan Mi, L. Ren, Li Guo, Ruixuan Guo, Ting Chen, Jiaxin Hu and 8 more. Nature Communications, 2020

2,883 citations recorded by the source corpus.

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.

Subfields: Infectious Diseases

View Paper: https://www.semanticscholar.org/paper/c5db08a4925ae08d69530ee3c2bb263f8fd9fca4

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In Infectious Diseases

Citations in the corpus

Structural and functional properties of SARS-CoV-2 spike protein: potential antivirus drug development for COVID-19 (2020, background): “Apilimod, a potent inhibitor of PIKfyve35, can significantly reduce the entry of SARS-CoV S pseudovirus into 293/hACE2 cells via early endosomes in a dose-dependent manner [49].”
Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies (2020, positive): “In vitro neutralization assays for SARS-CoV-2 include pseudoviruses based on HIV lentiviral particles (Chen et al., 2020; Crawford et al., 2020; Ou et al., 2020; Robbiani et al., 2020; Wu et al., 2020a), murine leukemia virus retroviral particles (Pinto et al., 2020; Quinlan et al., 2020), and…”
Protocol and Reagents for Pseudotyping Lentiviral Particles with SARS-CoV-2 Spike Protein for Neutralization Assays (2020, methodology): “For SARS-CoV-2, such pseudotyping has recently been reported using HIV-based lentiviral particles [4,27,37], MLV-based retroviral particles [12,38], and VSV [29,39–41].”
The Global Phosphorylation Landscape of SARS-CoV-2 Infection (2020, positive): “Apilimod, a PIKFYVE inhibitor, has been described in a recent study to have antiviral capacity (Ou et al., 2020).”
A Mouse Model of SARS-CoV-2 Infection and Pathogenesis (2020, positive): “Exogenous hACE2 has been demonstrated to inhibit SARS-CoV-2 infection in cell cultures (Monteil et al., 2020; Ou et al., 2020), and several monoclonal antibodies targeting RBDs of SARS-CoV or SARS-CoV-2 are being tested with in vitro cultures (Walls et al.”
Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology (2020, positive): “Brieﬂy, HEK293T cells were transfected with a SARS-CoV-2 S glycoprotein-encoding plasmid harboring the D 19 C-terminal truncation (Ou et al., 2020) using the X-tremeGENE HP DNA transfection reagent (Merk) according to the manufacturer’s instructions and then incubated at 37 C with 8% CO 2 for 24 h.”