Targeting Immunomodulation by Glutathione: A Possible Therapeutic Strategy against COVID-19

The severe acute respiratory syndrome coronavirus SARS-CoV-2, which causes COVID-19, has attracted the interest of the scientific community since 2019. In fact, in the majority of cases, COVID-19 results in a mildly symptomatic disease that needs no treatment. However, patients with comorbidities have an increased risk of severe manifestations of COVID-19. Although research progress in the field has been successfully accomplished, novel therapeutic strategies are still required. Treatment efforts are needed against the severe manifestations of the disease, such as the severe respiratory distress syndrome. The tripeptide glutathione could be a promising therapeutic approach against COVID-19. Glutathione is a multitarget agent that exhibits antiviral activity against SARS-CoV-2 and modulates the host response to SARS-CoV-2. Oxidative stress and glutathione deficiency have been implicated in the pathophysiology of severe COVID-19 disease. Thus, a possible therapeutic strategy could be the enhancement of the antioxidant defenses of the host through the treatment with nonenzymatic antioxidants. Apart from functioning as a scavenging agent, glutathione plays a central role in cellular signalling. As a redox regulator, glutathione also acts as a signalling molecule, thus modulating innate and T cell immunity, with implications for SARS-CoV-2 infection. Existing clinical data, although limited, provide evidence that the modulation of glutathione levels could be a preventive or adjunctive therapeutic strategy against SARS-CoV-2 infection.