GABA administration limits viral replication and pneumonitis in a mouse model of COVID-19

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Abstract

Despite the availability of vaccines for COVID-19, serious illness and death induced by coronavirus infection will remain a global health burden because of vaccination hesitancy, possible virus mutations, and the appearance of novel coronaviruses. Accordingly, there is a need for new approaches to limit severe illness stemming from coronavirus infections. Cells of the immune system and lung epithelia express receptors for GABA (GABA-Rs), a widely used neurotransmitter within the CNS. GABA-R agonists have anti-inflammatory effects and can limit acute lung injury. We previously showed that GABA treatment effectively reduced disease severity and death rates in mice following infection with a coronavirus (MHV-1) which provides a potentially lethal model of COVID-19. Here, we report that GABA treatment also reduced viral load in the lungs, suggesting that GABA-Rs may provide a new druggable target to limit pulmonary coronavirus replication. Histopathological analysis revealed that GABA treatment reduced lung inflammatory infiltrates and damages. Since GABA is safe for human consumption, inexpensive, and available worldwide, it is a promising candidate to help treat COVID-19.

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  1. SciScore for 10.1101/2021.02.09.430446: (What is this?)

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

    Table 1: Rigor

    Institutional Review Board StatementIACUC: The protocols for all experiments using vertebrate animals were approved by the Animal Research Committee at UCLA (approval # ARC-2020-122) and were carried out in compliance with the ARRIVE guidelines.
    RandomizationThe mice were immediately randomized and provided with plain water (controls) or water that contained GABA (20 mg/mL) as per (9, 39) for the entirety of the observation period.
    Blindingnot detected.
    Power Analysisnot detected.
    Sex as a biological variableMice: Female A/J mice (8 weeks in age) were purchased from the Jackson Laboratory and maintained in microisolator cages and fed with a standard diet and water ad libitum.
    Cell Line Authenticationnot detected.

    Table 2: Resources

    Experimental Models: Cell Lines
    SentencesResources
    Virus: MHV-1, DBT cells, and HeLa-CECAM1 were generously provided by Dr. Stanley Perlman (University of Iowa).
    HeLa-CECAM1
    suggested: None
    The viral titers in the supernatants were determined by endpoint dilution (40) in HeLa-CEACAM1 cells (85% confluent, 5 × 104 cells/well) using the Spearman-Kärber formula (41) to calculate 50% tissue culture infectious dose (TCID50).
    HeLa-CEACAM1
    suggested: None
    Experimental Models: Organisms/Strains
    SentencesResources
    Mice: Female A/J mice (8 weeks in age) were purchased from the Jackson Laboratory and maintained in microisolator cages and fed with a standard diet and water ad libitum.
    A/J
    suggested: RRID:IMSR_JAX:000646)
    Software and Algorithms
    SentencesResources
    Reagents: GABA (stock #A2129) was purchased from Millipore-Sigma (St. Louis, MO, USA).
    Millipore-Sigma
    suggested: None

    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.