UCLA Researchers Finds That Supplementation With The Amino Acid GABA Can Reduce SARS-CoV-2 Viral Load, COVID-19 Severity And Risk Of Mortality

COVID-19 Supplements: A new study led by researchers from University of California, Los Angeles - USA and also involving scientists from Keck School of Medicine of the University of Southern California - USA involving murine models has found that supplementation with the inexpensive amino acid GABA (Gamma-aminobutyric acid) can reduce SARS-CoV-2 viral loads and also help reduce COVID-19 severity and also risk of mortality.


 
Gamma-aminobutyric acid) or GABA is the chief inhibitory neurotransmitter in the developmentally mature mammalian central nervous system. Its principal role is reducing neuronal excitability throughout the nervous system. GABA is sold as a dietary supplement in many countries.
 
Both gamma-aminobutyric acid (GABA) and GABA-receptors (GABA-Rs) form a major neurotransmitter system in the brain.
 
GABA-receptors or GABA-Rs are also expressed by:
 
- 1) cells of the innate and adaptive immune system and act to inhibit their inflammatory activities, and
 
-2) lung epithelial cells and GABA-R agonists/potentiators have been observed to limit acute lung injuries.
 
Hence, these biological properties suggest that GABA-R agonists may have potential for treating COVID-19.
 
The study team previously reported that GABA-R agonist treatments protected mice from severe disease induced by infection with a lethal mouse coronavirus (MHV-1). https://pubmed.ncbi.nlm.nih.gov/34071034/
 
Since MHV-1 targets different cellular receptors and is biologically distinct from SARS-CoV-2, the study team decided to test GABA therapy in K18-hACE2 mice which develop severe pneumonitis with high lethality following SARS-CoV-2 infection.
 
The COVID-19 Supplements study findings showed that GABA treatment initiated immediately after SARS-CoV-2 infection, or 2 days later near the peak of lung viral load, reduced pneumonitis severity and death rates in K18-hACE2 mice.
 
Importantly, GABA-treated mice had reduced lung viral loads and displayed shifts in their serum cytokine/chemokine levels that are associated with better outcomes in COVID-19 patients. Thus, GABA-R activation had multiple effects that are also desirable for the treatment of COVID-19.
 
Co-author, Dr Jide Tian, a professor at Department of Molecular and Medical Pharmacology, University of California, Los Angeles, told Thailand Medical News, “The protective effects of GABA against two very different beta coronaviruses (SARS-CoV-2 and MHV-1) suggest that it may provide a generalizable off-the-shelf therapy to help treat diseases induced by new SARS-CoV-2 variants and novel coronaviruses that evade immune responses and antiviral medications. GABA is inexpensive, safe for human use, and stable at room temperature, making it an attractive candidate for testing in clinical trials.”
 
Dr Tian added, “We also discovered the potential of GABA-R agonists for limiting COVID-19-associated neuroinflammation.”
 
The study findings were published in the peer revi ewed journal: Frontiers In Immunology.
https://www.frontiersin.org/articles/10.3389/fimmu.2022.1007955/full
 
This is the first preclinical study in mice that model human COVID-19 that suggest that an inexpensive, readily available amino acid might limit the effects of the disease and provide a new off-the-shelf therapeutic option for infections with SARS-CoV-2 variants and perhaps future novel coronaviruses.
 
The study found that an amino acid called GABA, which is available over-the-counter in many countries, reduced disease severity, viral load in the lungs, and death rates in SARS-CoV-2-infected mice.
 
The research follows up on the study team’s previous finding that GABA consumption also protected mice from another lethal mouse coronavirus called MHV-1.
 
Importantly, in both cases, GABA treatment was effective when given just after infection or several days later near the peak of virus production. The protective effects of GABA against two different types of coronaviruses suggest that GABA may provide a generalizable therapy to help treat diseases induced by new SARS-CoV-2 variants and novel beta-coronaviruses.
 
Senior author Dr Daniel L. Kaufman, a researcher and professor in Molecular and Medical Pharmacology at the David Geffen School of Medicine at UCLA added, "SARS-CoV-2 variants and novel coronaviruses will continue to arise, and they may not be efficiently controlled by available vaccines and antiviral medications. Furthermore, the generation of new vaccines is likely to be much slower than the spread of new variants. Accordingly, new therapeutic options are needed to limit the severity of these infections.”
 
The study team’s previous study showed that GABA administration protected mice from developing severe disease after infection with a mouse coronavirus called MHV-1.
 
In order to more stringently test the potential of GABA as a therapy for COVID-19, they studied transgenic mice that when infected with SARS-CoV-2 develop severe pneumonia with a high mortality rate.
 
Dr Kaufman added, "If our observations of the protective effects of GABA therapy in SARS-CoV-2-infected mice are confirmed in clinical trials, GABA could provide an off-the-shelf treatment to help ameliorate infections with SARS-CoV-2 variants. GABA is inexpensive and stable at room temperature, which could make it widely and easily accessible, and especially beneficial in developing countries."
 
The study team said that GABA and GABA receptors are most often thought of as a major neurotransmitter system in the brain. Years ago, they, as well as other researchers, found that cells of the immune system also possessed GABA receptors and that the activation of these receptors inhibited the inflammatory actions of immune cells. Taking advantage of this property, the study team reported in a series of studies that GABA administration inhibited autoimmune diseases such as type 1 diabetes, multiple sclerosis, and rheumatoid arthritis in mouse models of these ailments.
 
May other researchers who study gas anesthetics have found that lung epithelial cells also possess GABA receptors and that drugs that activate these receptors could limit lung injuries and inflammation in the lung.
 
Important, the dual actions of GABA in inflammatory immune cells and lung epithelial cells, along with its safety for clinical use, made GABA a theoretically appealing candidate for limiting the overreactive immune responses and lung damage due to coronavirus infection.
 
The study team administered GABA to the mice just after infection with SARS-CoV-2, or two days later when the virus levels are near their peak in the mouse lungs.
 
Although the vast majority of untreated mice did not survive this infection, those given GABA just after infection, or two days later, had less illness severity and a lower mortality rate over the course of the study.
 
Also, treated mice also displayed reduced levels of virus in their lungs and changes in circulating immune signaling molecules, known as cytokines and chemokines, toward patterns that were associated with better outcomes in COVID-19 patients.
 
Hence, GABA receptor activation had multiple beneficial effects in this mouse model that are also desirable for the treatment of COVID-19.
 
The study team hope that their new findings will provide a springboard for testing the efficacy of GABA treatment in clinical trials with COVID-19 patients.
 
As GABA has an excellent safety record, is inexpensive and available worldwide, clinical trials of GABA treatment for COVID-19 can be initiated rapidly.
 
The study team also suspect that the anti-inflammatory properties of GABA-receptor activating drugs may also be useful for limiting inflammation in the central nervous system that is associated with long-COVID.
 
In fact, this approach was very successful in their previous studies of therapeutics for multiple sclerosis in mice, a disease which is caused by an inflammatory autoimmune response in the brain.
https://pubmed.ncbi.nlm.nih.gov/20133656/
 
The study team speculate that such drugs may reduce both the deleterious effects of coronavirus infection in the periphery and limit inflammation in the central nervous system.
 
To date however, there has been no pharmaceutical interest pursuing GABA therapy for COVID-19, presumably because it is not patentable and widely available as a dietary supplement. The study team hope for federal funding to continue this line of study.
 
The study team emphasize that unless clinical trials are conducted and GABA is approved for treating COVID-19 by relevant governing bodies, it should not be consumed for the treatment of COVID-19 since it could pose health risks, such as dampening beneficial immune or physiological responses.
 
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