Kidney injury molecule-1 is a potential receptor for SARS-CoV-2

  1. Chen Yang
  2. Yu Zhang
  3. Xia Zeng
  4. Huijing Chen
  5. Yuchen Chen
  6. Dong Yang
  7. Ziwei Shen
  8. Xiaomu Wang
  9. Xinran Liu
  10. Mingrui Xiong
  11. Hong Chen
  12. Kun Huang

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Abstract

COVID-19 patients present high incidence of kidney abnormalities, which are associated with poor prognosis and mortality. The identification of SARS-CoV-2 in the kidney of COVID-19 patients suggests renal tropism of SARS-CoV-2. However, whether there is a specific target of SARS-CoV-2 in the kidney remains unclear. Herein, by using in silico simulation, coimmunoprecipitation, fluorescence resonance energy transfer, fluorescein isothiocyanate labeling, and rational design of antagonist peptides, we demonstrate that kidney injury molecule-1 (KIM1), a molecule dramatically upregulated upon kidney injury, binds with the receptor-binding domain (RBD) of SARS-CoV-2 and facilitates its attachment to cell membrane, with the immunoglobulin variable Ig-like (Ig V) domain of KIM1 playing a key role in this recognition. The interaction between SARS-CoV-2 RBD and KIM1 is potently blockaded by a rationally designed KIM1-derived polypeptide AP2. In addition, our results also suggest interactions between KIM1 Ig V domain and the RBDs of SARS-CoV and MERS-CoV, pathogens of two severe infectious respiratory diseases. Together, these findings suggest KIM1 as a novel receptor for SARS-CoV-2 and other coronaviruses. We propose that KIM1 may thus mediate and exacerbate the renal infection of SARS-CoV-2 in a ‘vicious cycle’, and KIM1 could be further explored as a therapeutic target.

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  1. Version published to 10.1093/jmcb/mjab003
  2. ScreenIT

    SciScore for 10.1101/2020.10.09.334052: (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 variableFor cisplatin-induced AKI, 30 mg/kg bodyweight cisplatin was injected intraperitoneally into 8-week-old male mice, and mice were sacrificed 3 days later.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Anti-Mouse-IgG (H&L) antibody (p/n 18-8817-33) and anti-Rabbit-IgG (H&L) antibody (p/n 18-8817-33) were obtained from RockLand (Philadelphia, PA).
    Anti-Mouse-IgG (H&L
    suggested: None
    anti-Rabbit-IgG (H&L
    suggested: None
    Antibodies against KIM1 (NBP1-76701, Novus Biologicals, New York, NY), Flag (F1804, Sigma), HA (H6908, Sigma), ACE2 (21115-1-AP, Proteintech, Wuhan, China) were used.
    KIM1
    suggested: (Novus Cat# NBP1-76701, RRID:AB_11037459)
    NBP1-76701
    suggested: (Novus Cat# NBP1-76701, RRID:AB_11037459)
    HA
    suggested: (Sigma-Aldrich Cat# H6908, RRID:AB_260070)
    ACE2
    suggested: (Proteintech Cat# 21115-1-AP, RRID:AB_10732845)
    21115-1-AP, Proteintech, Wuhan, China
    suggested: None
    Experimental Models: Cell Lines
    SentencesResources
    2.8 Co-immunoprecipitation (Co-IP): Transfected HK-2/HEK293T cells were lysed in 1 mL pre-lysis buffer.
    HK-2/HEK293T
    suggested: None
    2.11 Confocal microscopy: Transfected HEK293T cells (5 × 106) or HK-2 cells (1 × 107) were incubated with free FITC or FITC-SARS-CoV-2-RBD for 2 h.
    HEK293T
    suggested: None
    HK-2
    suggested: None
    Experimental Models: Organisms/Strains
    SentencesResources
    2.5 AKI mouse models and qPCR: I/R injury was performed on C57BL/6 mice as we previously described21.
    C57BL/6
    suggested: None
    Software and Algorithms
    SentencesResources
    Analyses were performed with EXCEL 2017 and GraphPad Prism 8.0.
    GraphPad Prism
    suggested: (GraphPad Prism, RRID:SCR_002798)

    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 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:
    • 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.

  3. Version published to 10.1101/2020.10.09.334052v1 on bioRxiv