GABA administration prevents severe illness and death following coronavirus infection in mice
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Abstract
There is an urgent need for new treatments to prevent and ameliorate severe illness and death induced by SARS-CoV-2 infection in COVID-19 patients. The coronavirus mouse hepatitis virus (MHV)-1 causes pneumonitis in mice which shares many pathological characteristics with human SARS-CoV infection. Previous studies have shown that the amino acid gamma-aminobutyric acid (GABA) has anti-inflammatory effects. We tested whether oral treatment with GABA could modulate the MHV-1 induced pneumonitis in susceptible A/J mice. As expected, MHV-1-inoculated control mice became severely ill (as measured by weight loss, clinical score, and the ratio of lung weight to body weight) and >60% of them succumbed to the infection. In contrast, mice that received GABA immediately after MHV-1 inoculation became only mildly ill and all of them recovered. When GABA treatment was initiated after the appearance of illness (3 days post-MHV-1 infection), we again observed that GABA treatment significantly reduced the severity of illness and greatly increased the frequency of recovery. Therefore, the engagement of GABA receptors (GABA-Rs) prevented the MHV-1 infection-induced severe pneumonitis and death in mice. Given that GABA-R agonists, like GABA and homotaurine, are safe for human consumption, stable, inexpensive, and available worldwide, they are promising candidates to help prevent severe illness stemming from SARS-CoV-2 infection and other coronavirus strains.
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SciScore for 10.1101/2020.10.04.325423: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: The protocols for all experiments using vertebrate animals were approved by the Animal Research Committee at UCLA. Reagents: GABA was purchased from Millipore-Sigma (stock # A2129, St. Louis, MO, USA). Randomization The mice were immediately randomized and treated (or not treated) with GABA, as described below. Blinding not detected. Power Analysis not detected. Sex as a biological variable Mice: Female A/J mice (7 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 Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Viru… SciScore for 10.1101/2020.10.04.325423: (What is this?)
Please note, not all rigor criteria are appropriate for all manuscripts.
Table 1: Rigor
Institutional Review Board Statement IACUC: The protocols for all experiments using vertebrate animals were approved by the Animal Research Committee at UCLA. Reagents: GABA was purchased from Millipore-Sigma (stock # A2129, St. Louis, MO, USA). Randomization The mice were immediately randomized and treated (or not treated) with GABA, as described below. Blinding not detected. Power Analysis not detected. Sex as a biological variable Mice: Female A/J mice (7 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 Authentication not detected. Table 2: Resources
Experimental Models: Cell Lines Sentences Resources Virus: MHV-1, DBT cells, and HeLa-CECAM1 were generously provided by Dr. Stanley Perlman (University of Iowa). HeLa-CECAM1suggested: NoneExperimental Models: Organisms/Strains Sentences Resources Viral infection and GABA treatment: At 8 weeks in age, female A/J mice were anesthetized and inoculated intranasally with 5000 PFU MHV-1 in 50 μl cold Dulbecco’s modified Eagle’s medium (DMEM). A/Jsuggested: NoneResults 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:
Identifier Status Title NCT02002130 Active, not recruiting The Use of Glutamic Acid Decarboxylase (GAD) and Gamma-Amino… NCT03635437 Recruiting Evaluation of Safety and Diabetes Status Upon Oral Treatment… NCT03721991 Unknown status GABA Treatment in Subjects With Type 1 Diabetes NCT04375020 Completed GABA and Beta-cell Regeneration 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.
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