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

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

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Abstract

COVID-19 patients present high incidence of kidney abnormalities, which are associated with poor prognosis and high mortality. Identification of SARS-CoV-2 in kidney of COVID-19 patients suggests renal tropism and direct infection. Presently, it is generally recognized that SARS-CoV-2 initiates invasion through binding of receptor-binding domain (RBD) of spike protein to host cell-membrane receptor ACE2, however, whether there is additional target of SARS-CoV-2 in kidney remains unclear. Kidney injury molecule-1 (KIM1) is a transmembrane protein that drastically up-regulated after renal injury. Here, binding between SARS-CoV2-RBD and the extracellular Ig V domain of KIM1 was identified by molecular simulations and co-immunoprecipitation, which was comparable in affinity to that of ACE2 to SARS-CoV-2. Moreover, KIM1 facilitated cell entry of SARS-CoV2-RBD, which was potently blockaded by a rationally designed KIM1-derived polypeptide. Together, the findings suggest KIM1 may mediate and exacerbate SARS-CoV-2 infection in a ‘vicious cycle’, and KIM1 could be further explored as a therapeutic target.

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  1. 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.

  2. Version published to 10.1101/2020.10.09.334052 on bioRxiv