GABAA-Receptor Agonists Limit Pneumonitis and Death in Murine Coronavirus-Infected Mice

Viruses. 2021 May 23;13(6):966. doi: 10.3390/v13060966.

Abstract

There is an urgent need for new approaches to limit the severity of coronavirus infections. Many cells of the immune system express receptors for the neurotransmitter γ-aminobutyric acid (GABA), and GABA-receptor (GABA-R) agonists have anti-inflammatory effects. Lung epithelial cells also express GABA-Rs, and GABA-R modulators have been shown to limit acute lung injuries. There is currently, however, no information on whether GABA-R agonists might impact the course of a viral infection. Here, we assessed whether clinically applicable GABA-R agonists could be repurposed for the treatment of a lethal coronavirus (murine hepatitis virus 1, MHV-1) infection in mice. We found that oral GABA administration before, or after the appearance of symptoms, very effectively limited MHV-1-induced pneumonitis, severe illness, and death. GABA treatment also reduced viral load in the lungs, suggesting that GABA-Rs may provide a new druggable target to limit coronavirus replication. Treatment with the GABAA-R-specific agonist homotaurine, but not the GABAB-R-specific agonist baclofen, significantly reduced the severity of pneumonitis and death rates in MHV-1-infected mice, indicating that the therapeutic effects were mediated primarily through GABAA-Rs. Since GABA and homotaurine are safe for human consumption, they are promising candidates to help treat coronavirus infections.

Keywords: COVID-19; GABA; GABA-receptors; mouse hepatitis virus (MHV); therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Coronavirus Infections / drug therapy*
  • Coronavirus Infections / mortality
  • Coronavirus Infections / virology
  • GABA-A Receptor Agonists / therapeutic use*
  • Lung / drug effects
  • Lung / pathology
  • Lung / virology
  • Mice
  • Murine hepatitis virus / drug effects*
  • Murine hepatitis virus / pathogenicity
  • Pneumonia / drug therapy*
  • Pneumonia / mortality
  • Pneumonia / virology
  • Severity of Illness Index
  • Treatment Outcome
  • Viral Load / drug effects
  • Weight Loss / drug effects
  • gamma-Aminobutyric Acid / therapeutic use

Substances

  • GABA-A Receptor Agonists
  • gamma-Aminobutyric Acid