Boosting Immunity: Synergistic Antiviral Effects of Luteolin, Vitamin C, Magnesium, and Zinc Against SARS-CoV-2 3CLpro

Vitamin C has been identified by the European Food Safety Authority (EFSA) as having sufficient evidence for a causal relationship between intake and optimal immune system function13-15. Vitamin C plays a key role in the immune system, supporting the production and function of leukocytes, or white blood cells, which defend against infection and disease, including the production of lymphocytes, which make antibodies, and enhancing phagocytosis, the process by which immune system cells ingest and destroy viruses and infected cells. Vitamin C is an antioxidant, protecting cells from damage caused by free radicals. Vitamin C inhibits SARS-CoV-2 3CL^pro5,9, inhibits SARS-CoV-2 infection by reducing ACE2 levels in a dose-dependent manner10, and may limit COVID-19 induced cardiac damage by acting as an antioxidant and potentially reducing the reactive oxygen species (ROS) production induced by the spike protein that contributes to the activation of profibrotic pathways7. Vitamin C reduces inflammation, oxidative stress, and NETosis, supporting immune function and vascular protection16. Intracellular levels of vitamin C decline during COVID-19 hospitalization suggesting ongoing utilization and depletion of vitamin C17. Threonic acid, a metabolite of vitamin C, is lower in mild and severe cases, consistent with increased need for and metabolization of vitamin C with moderate infection, but more limited ability to produce threonic acid in severe infection due to depletion or existing lower levels of vitamin C18. Symptomatic COVID-19 is associated with a lower frequency of natural killer (NK) cells, and vitamin C has been shown to improve NK cell numbers and functioning19,20.