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

• Main Authors: Jide Tian, Blake Middleton, Daniel L. Kaufman
• Format: Article
• Language: English
• Published: MDPI AG 2021-05-01
• Series: Viruses
• Subjects: GABA; GABA-receptors; mouse hepatitis virus (MHV); therapy; COVID-19
• Online Access: https://www.mdpi.com/1999-4915/13/6/966

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 GABA_A-R-specific agonist homotaurine, but not the GABA_B-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 GABA_A-Rs. Since GABA and homotaurine are safe for human consumption, they are promising candidates to help treat coronavirus infections.