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- Title
GABA A -Receptor Agonists Limit Pneumonitis and Death in Murine Coronavirus-Infected Mice.
- Authors
Tian, Jide; Middleton, Blake; Kaufman, Daniel L.
- 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.
- Subjects
GABA agonists; VIRAL hepatitis; VIRUS diseases; CORONAVIRUS disease treatment; COVID-19; RIBAVIRIN
- Publication
Viruses (1999-4915), 2021, Vol 13, Issue 6, p966
- ISSN
1999-4915
- Publication type
Article
- DOI
10.3390/v13060966