Human basigin (CD147) does not directly interact with SARS-CoV-2 spike glycoprotein

  1. Robert J. Ragotte
  2. David Pulido
  3. Francesca R. Donnellan
  4. Giacomo Gorini
  5. Hannah Davies
  6. Juliane Brun
  7. Lloyd D. W. King
  8. Katherine Skinner
  9. Simon J. Draper

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Abstract

Basigin, or CD147, has been reported as a co-receptor used by SARS-CoV-2 to invade host cells. Basigin also has a well-established role in Plasmodium falciparum malaria infection of human erythrocytes where it is bound by one of the parasite’s invasion ligands, reticulocyte binding protein homolog 5 (RH5). Here, we sought to validate the claim that the receptor binding domain (RBD) of SARS-CoV-2 spike glycoprotein can form a complex with basigin, using RH5-basigin as a positive control. Using recombinantly expressed proteins, size exclusion chromatography and surface plasmon resonance, we show that neither RBD nor full-length spike glycoprotein bind to recombinant human basigin (either expressed in E. coli or mammalian cells). Given the immense interest in SARS-CoV-2 therapeutic targets, we would caution the inclusion of basigin in this list on the basis of its reported direct interaction with SARS-CoV-2 spike glycoprotein.

Importance

Reducing the mortality and morbidity associated with COVID-19 remains a global health priority. Critical to these efforts is the identification of host factors that are essential to viral entry and replication. Basigin, or CD147, was previously identified as a possible therapeutic target based on the observation that it may act as a co-receptor for SARS-COV-2, binding to the receptor binding domain of the spike protein. Here, we show that there is no direct interaction between the RBD and basigin, casting doubt on its role as a co-receptor and plausibility as a therapeutic target.

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  1. ScreenIT

    SciScore for 10.1101/2021.02.22.432402: (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
    Human IgG1 CR3022 antibody (28) (GenBank: ABA54613.1 and ABA54614.1) was expressed from heavy and light chain AbVec expression vectors in Expi293™ cells (Thermo Fisher Scientific).
    Human IgG1 CR3022 antibody
    suggested: (Imported from the IEDB Cat# CR3022, RRID:AB_2848080)
    Human IgG1
    suggested: (Imported from the IEDB Cat# CR3022, RRID:AB_2848080)
    Experimental Models: Cell Lines
    SentencesResources
    This construct was expressed as a secreted protein by a stable Drosophila S2 cell line (30) and affinity purified using C-tag affinity resin (Thermo Fisher Scientific) followed by a size-exclusion chromatography polishing step in 20 mM Tris, 150 mM NaCl, pH 7.4.
    S2
    suggested: DGRC Cat# 150, RRID:CVCL_Z831)

    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: We found the following clinical trial numbers in your paper:

    IdentifierStatusTitle
    NCT04275245RecruitingClinical Study of Anti-CD147 Humanized Meplazumab for Inject…

    Results from Barzooka: We did not find any issues relating to the usage of bar graphs.

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

    Results from rtransparent:
    • No conflict of interest statement was detected. If there are no conflicts, we encourage authors to explicit state so.
    • 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 10.1101/2021.02.22.432402 on bioRxiv