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.

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.

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