Researchers from UCLA’s Department of Molecular and Medical Pharmacology have identified and validated a therapeutic target and an accompanying drug class which ameliorates illness and death due to Coronavirus infection.
BACKGROUND
There remains an urgent need for treatments that can reduce the symptoms for those infected by SARS-CoV-2, its future variants, and other new coronaviruses for which vaccines do not exist. There are currently a variety of therapeutic options available that include: monoclonal antibodies (e.g., etesevimab), anti-inflammatory drugs (e.g., dexamethasone), and immunomodulatory agents (e.g., baricitinib). However, the clinical efficacy of these approaches is limited. New therapeutics are needed to both regulate inappropriate immune responses to the infection and to protect lung epithelial cells from damage.
INNOVATION
UCLA researchers have identified a targetable receptor on both immune cells and lung epithelial cells which when activated greatly reduced the severity and lethality of murine Coronavirus infection in in vivo mouse models. The UCLA researchers studied mice infected with mouse hepatitis virus (MHV)-1, which like SARs-CoV and SARS-CoV-2 is a pneumotropic beta-coronavirus of the group 2 lineage and an accepted model for SARS-Cov2 infection. The UCLA researchers discovered a class of compounds, and a potent lead, that activates the receptor and oral treatment with the receptor’s agonists greatly reduced the severity of illness, lung edema and death rate due to MHV-1 infection even when the drug was given after the appearance of clinical symptoms. Furthermore, treatment reduced viral load in the lungs. Due to the stability of the activating compounds, it is possible to vary the delivery approach, thus making it a valid option for shipment and administration in remote locations.
POTENTIAL APPLICATIONS:
● Treatment of Coronavirus infected patients
● Preemptive treatment for at risk populations
● Reduce respiratory inflammation and ARDS
● Modulating inappropriate immune responses
● Reduced viral loads and damage in the lungs
ADVANTAGES:
● Reduction of symptoms and morbidity attributed to Coronavirus
● Compound can be delivered through various routes include oral, sublingual, and aerosol
● Effective when given after symptoms arise
DEVELOPMENT-TO-DATE: Compound has been successfully tested in in vivo mouse model. Additional testing is still underway.
RELATED PAPERS:
- Tian, J., Middleton, B. & Kaufman, D. L. GABAA-Receptor Agonists Limit Pneumonitis and Death in Murine Coronavirus-Infected Mice. Viruses 13, 966 (2021)
- Jide Tian, Barbara J. Dillion, Jill Henley, Lucio Comai, Daniel L. Kaufman GABA-receptors are a new druggable target for limiting disease severity, lung viral load, and death in SARS-CoV-2 infected mice, bioRxiv 2022.06.07.494579; doi: https://doi.org/10.1101/2022.06.07.494579
PRESS RELEASE:
https://www.uclahealth.org/news/preliminary-mouse-study-suggests-readily-available-amino