NRP1 and furin as putative mediators of SARS-CoV-2 entry into human brain cells

  1. Ashutosh Kumar
  2. Ravi K. Narayan
  3. Sujeet Kumar
  4. Vikas Pareek
  5. Chiman Kumari
  6. Rakesh K. Jha
  7. Pranav Prasoon

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Abstract

COVID-19 has prominent neurological manifestations including psychiatric symptoms, indicating significant synaptic pathology. Surprisingly, existing evidence suggests negligible expression of the key SARS-CoV-2 host cell entry mediators ACE2 and TMPRSS2 in human brain, which complicates understanding of the pathomechanisms of the neuropsychiatric manifestations in COVID-19. Recent studies suggested that an alternative host-cell entry receptor, NRP1 , can mediate entry of furin cleaved SARS-CoV-2 spike proteins into the host cells. However, the role of NRP1 and furin in mediating SARS-CoV-2 entry in human brain cells has been least explored and remains a lacuna in the literature. We performed an in silico analysis of the transcriptomic and proteomic expressions of SARS-CoV-2 host-cell entry receptors and associated tissue proteases in human brain tissue, using the publically available databases. Based on the expression analysis, SARS-CoV-2 entry in human brain cells is likely to be mediated through NRP1 and furin .

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  1. ScreenIT

    SciScore for 10.1101/2022.01.19.476893: (What is this?)

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

    Table 1: Rigor

    EthicsIRB: IHC: The specimens containing normal-tissue were collected in accordance with approval from the local ethics committee.
    Sex as a biological variablenot detected.
    Randomizationnot detected.
    Blindingnot detected.
    Power Analysisnot detected.

    Table 2: Resources

    Antibodies
    SentencesResources
    Antibodies against human ACE2 (HPA000288, CAB026174), NRP1 (HPA030278, CAB004511), TMPRSS2 (HPA035787), and furin (CAB009499) were used.
    human ACE2
    suggested: (Sigma-Aldrich Cat# HPA000288, RRID:AB_1078160)
    NRP1
    suggested: (Atlas Antibodies Cat# HPA030278, RRID:AB_10601976)
    TMPRSS2
    suggested: (Sigma-Aldrich Cat# HPA035787, RRID:AB_2674782)
    HPA035787
    suggested: (Sigma-Aldrich Cat# HPA035787, RRID:AB_2674782)
    furin (CAB009499
    suggested: None
    Software and Algorithms
    SentencesResources
    We performed in silico analysis of mRNA and protein expressions of ACE2, NRP1, TMPRSS2, and furin in human brain immune components using the tissue transcriptome and immunohistochemistry (IHC) data available in Human Brain Atlas (HBA), a sub-section of Human Protein Atlas (HPA) (https://www.proteinatlas.org/).
    https://www.proteinatlas.org/
    suggested: (HPA, RRID:SCR_006710)
    Experion automated electrophoresis system (Bio-Rad Laboratories, Hercules, CA, USA) with the standard-sensitivity RNA chip or an Agilent 2100 Bioanalyzer system with the RNA 6000 Nano Labchip Kit (Agilent Biotechnologies, Palo Alto, USA) was used to analyze the extracted RNA samples.
    Bio-Rad Laboratories
    suggested: (Bio-Rad Laboratories, RRID:SCR_008426)
    Agilent Biotechnologies
    suggested: None
    Kallisto v0.43.1 (https://pachterlab.github.io/kallisto/about) was used for estimation of the transcript abundance.
    Kallisto
    suggested: (kallisto, RRID:SCR_016582)

    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: We detected the following sentences addressing limitations in the study:
    Limitations: For certain brain regions proteomic expression data were not available to corroborate transcriptomic expressions of the studied markers. Further, the study didn’t employ any experimental evidence to corroborate the findings derived from the in silico analysis. The in situ/in vivo studies are warranted to validate our findings.

    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.

    Results from scite Reference Check: We found no unreliable references.

    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 10.1101/2022.01.19.476893v1 on bioRxiv
  3. Version published to 10.1089/regen.2022.0047