Receptor utilization of angiotensin converting enzyme 2 (ACE2) indicates a narrower host range of SARS-CoV-2 than that of SARS-CoV

  1. Ye Qiu
  2. Qiong Wang
  3. Jin-Yan Li
  4. Ce-Heng Liao
  5. Zhi-Jian Zhou
  6. Xing-Yi Ge

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Abstract

Coronavirus pandemics have become a huge threat to the public health worldwide in the recent decades. Typically, SARS-CoV caused SARS pandemic in 2003 and SARS-CoV-2 caused the COVID-19 pandemic recently. Both viruses have been reported to originate from bats. Thus, direct or indirect interspecies transmission from bats to humans is required for the viruses to cause pandemics. Receptor utilization is a key factor determining the host range of viruses which is critical to the interspecies transmission. Angiotensin converting enzyme 2 (ACE2) is the receptor of both SARS-CoV and SARS-CoV-2, but only ACE2s of certain animals can be utilized by the viruses. Here, we employed pseudovirus cell-entry assay to evaluate the receptor-utilizing capability of ACE2s of 20 animals by the two viruses and found that SARS-CoV-2 utilized less ACE2s than SARS-CoV, indicating a narrower host range of SARS-CoV-2. Meanwhile, pangolin CoV, another SARS-related coronavirus highly homologous to SARS-CoV-2 in its genome, yet showed similar ACE2 utilization profile with SARS-CoV rather than SARS-CoV-2. To clarify the mechanism underlying the receptor utilization, we compared the amino acid sequences of the 20 ACE2s and found 5 amino acid residues potentially critical for ACE2 utilization, including the N-terminal 20 th and 42 nd amino acids that may determine the different receptor utilization of SARS-CoV, SARS-CoV-2 and pangolin CoV. Our studies promote the understanding of receptor utilization of pandemic coronaviruses, potentially contributing to the virus tracing, intermediate host screening and epidemic prevention for pathogenic coronaviruses.

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  1. ScreenIT

    SciScore for 10.1101/2020.06.13.149930: (What is this?)

    Please note, not all rigor criteria are appropriate for all manuscripts.

    Table 1: Rigor

    Institutional Review Board Statementnot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variablenot detected.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    For detection of S protein, the membrane was incubated with anti-HA tag mouse monoclonal antibody (bimake, USA, 1:2000), and the bound antibodies were detected by Horseradish Peroxidase (HRP)-conjugated goat anti-mouse IgG (Abbkine, China, 1:5,000).
    anti-HA
    suggested: None
    anti-mouse IgG
    suggested: None
    For detection of HIV-1 p24 in supernatants, monoclonal antibody against HIV p24 (p24 MAb) was used as the primary antibody at a dilution of 1:8,000, followed by incubation with HRP-conjugated goat anti-mouse IgG at the same dilution.
    HIV-1
    suggested: None
    HIV
    suggested: None
    To detect the expression of 20 ACE2s in HeLa cells, Mouse anti-His tag monoclonal antibody (Bioworld, USA, 1:5000) was used as the first antibody, followed by incubation with HRP-conjugated goat anti-mouse IgG at the same dilution.
    anti-His tag
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    Cell lines and plasmids: HEK293T and HeLa cells were obtained from the American Tissue Culture Collection and cultured in Dulbecco’s modified Eagle medium (DMEM) (Gibco, USA) supplemented with 10% fetal bovine serum (FBS) in a humidified 5% CO2 incubator at 37°C.
    HEK293T
    suggested: None
    To detect the expression of 20 ACE2s in HeLa cells, Mouse anti-His tag monoclonal antibody (Bioworld, USA, 1:5000) was used as the first antibody, followed by incubation with HRP-conjugated goat anti-mouse IgG at the same dilution.
    HeLa
    suggested: None
    Software and Algorithms
    SentencesResources
    Phylogenetic analysis: Multiple sequence alignment was performed for the whole aa sequences of ACEs using MAFFT with a local alignment strategy FFT-NS-2.
    MAFFT
    suggested: (MAFFT, RRID:SCR_011811)
    The phylogenetic tree was constructed by MEGA7 using the neighbor-joining (NJ) method with 1,000 bootstrap replicates and visualized using FigTree.
    MEGA7
    suggested: None
    FigTree
    suggested: (FigTree, RRID:SCR_008515)

    Results from OddPub: We did not detect open data. We also did not detect open code. Researchers are encouraged to share open data when possible (see Nature blog).

    Results from LimitationRecognizer: An explicit section about the limitations of the techniques employed in this study was not found. We encourage authors to address study limitations.

    Results from TrialIdentifier: No clinical trial numbers were referenced.

    Results from Barzooka: We found bar graphs of continuous data. We recommend replacing bar graphs with more informative graphics, as many different datasets can lead to the same bar graph. The actual data may suggest different conclusions from the summary statistics. For more information, please see Weissgerber et al (2015).

    Results from JetFighter: We did not find any issues relating to colormaps.

    Results from rtransparent:
    • Thank you for including a conflict of interest statement. Authors are encouraged to include this statement when submitting to a journal.
    • Thank you for including a funding statement. Authors are encouraged to include this statement when submitting to a journal.
    • No protocol registration statement was detected.

    About SciScore

    SciScore is an automated tool that is designed to assist expert reviewers by finding and presenting formulaic information scattered throughout a paper in a standard, easy to digest format. SciScore checks for the presence and correctness of RRIDs (research resource identifiers), and for rigor criteria such as sex and investigator blinding. For details on the theoretical underpinning of rigor criteria and the tools shown here, including references cited, please follow this link.

  2. Version published to 10.1101/2020.06.13.149930 on bioRxiv