Chemists at the University of North Carolina at Greensboro have published a paper in the journal Antioxidants, unveiling a novel understanding of how dietary selenium impacts the severity of COVID-19. Their research expands upon earlier findings, pinpointing six proteins within the host that might be targeted by SARS-CoV-2 by confirming that three selenoproteins, known for their roles in antioxidant defence and antiviral activities, were indeed cleaved at predicted sites. They further discovered that the virus’s protease attacks and possibly deactivates glutamate-cysteine ligase catalytic subunit (GCLC), a crucial enzyme in glutathione synthesis. This action undermines the body’s antioxidant defence by impairing a vital selenoprotein’s function and reducing glutathione levels observed in patients with COVID-19, thereby compromising the immune response and facilitating more efficient viral replication.
Ethan W. Taylor, a professor of biomedical chemistry at UNCG and co-author of the study, highlighted the significance of this discovery. He stated that it is the inaugural demonstration of a virus actively targeting human selenium-dependent proteins. He suggested that selenium’s role in biochemistry might be pivotal for enhancing immune defences against COVID.
The study’s authors, including Ignacio A. Gallardo, Daniel A. Todd, Stella T. Lima, Jonathan R. Checkan, Norman H. Chu, and Taylor, leveraged prior research that correlated dietary selenium intake with the outcomes of viral infections. Their current work experimentally verified that the main protease of SARS-CoV-2 could cleave targets in four out of six identified host proteins, including selenoproteins such as thioredoxin reductase 1 (TXNRD1), selenoprotein F, and selenoprotein P, in addition to GCLC. They observed that the cleavage of the full-length TXNRD1 protein by the viral protease led to a loss of its antioxidant functionality by severing its C-terminal redox centre.
Taylor elaborated on the mechanism, noting that the proteins targeted for cleavage by the virus play significant roles in antioxidation and antiviral defence. Reducing disulfide bonds can deactivate viral proteins, which could amplify viral infectivity by undermining the function of several essential proteins.
The research also posits that the virus’s strategy may extend to impeding DNA synthesis to conserve ribonucleotide pools, thereby enhancing RNA synthesis and viral replication. This revelation points to the necessity for further exploration into the clinical benefits of selenium supplementation and various dietary sulfur compounds that serve as glutathione precursors. Such compounds include N-acetyl cysteine (NAC), the combination of NAC and glycine, or gamma-glutamylcysteine (GGC), as well as potential substitutes like alpha lipoic acid (ALA) that mimic glutathione’s effects. This direction could yield new adjunctive treatments for COVID-19, offering symptomatic relief to patients.
More information: Ignacio A. Gallardo, Daniel A. Todd, Stella T. Lima, Jonathan R. Chekan, Norman H. Chiu and Ethan Will Taylor. SARS-CoV-2 Main Protease Targets Host Selenoproteins and Glutathione Biosynthesis for Knockdown via Proteolysis, Potentially Disrupting the Thioredoxin and Glutaredoxin Redox Cycles, Antioxidants. DOI: 10.3390/antiox12030559
Journal information: Antioxidants Provided by University of North Carolina Greensboro
