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Electrophoretic Delivery of γ-aminobutyric Acid GABA into Epileptic Focus Prevents Seizures in Mice
Published on: May 16, 2019
GABA administration prevents severe illness and death following coronavirus infection in mice
Jide Tian1, Blake Middleton1, Daniel L Kaufman1
1Department of Molecular and Medical Pharmacology, University of California, Los Angeles, California.
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.
Insights
Gamma-aminobutyric acid (GABA) treatment significantly reduced illness and prevented death in mice infected with a coronavirus. GABA agonists show promise for preventing severe illness from SARS-CoV-2 and other coronaviruses.
Area of Science:
- Virology
- Immunology
- Pharmacology
Background:
- Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes COVID-19, necessitating novel treatments.
- Mouse hepatitis virus (MHV)-1 infection in mice mimics human SARS-CoV-1 infection, presenting a valuable model for studying viral pneumonitis.
- Gamma-aminobutyric acid (GABA), an amino acid, exhibits anti-inflammatory properties.
Approach:
- Investigated the efficacy of oral GABA treatment in mitigating MHV-1-induced pneumonitis in susceptible A/J mice.
- Administered GABA immediately post-infection and at 3 days post-infection to assess its therapeutic window.
- Monitored disease severity through weight loss, clinical scores, and lung-to-body weight ratios.
Key Points:
- MHV-1 infection led to severe illness and mortality (>60%) in untreated control mice.
- GABA treatment initiated immediately after MHV-1 inoculation resulted in mild illness and full recovery.
- Delayed GABA administration (3 days post-infection) also significantly reduced illness severity and improved recovery rates.
- Engagement of GABA receptors (GABA-Rs) was crucial in preventing severe pneumonitis and death.
Conclusions:
- GABA and its receptor agonists are safe, stable, inexpensive, and globally available.
- GABA-R agonists represent promising therapeutic candidates for preventing severe illness associated with SARS-CoV-2 and other coronavirus infections.

