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Abstract
Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) represents an emergent global threat which is straining worldwide healthcare capacity. As of May 27th, the disease caused by SARS-CoV-2 (COVID-19) has resulted in more than 340,000 deaths worldwide, with 100,000 deaths in the US alone. It is imperative to study and develop pharmacological treatments suitable for the prevention and treatment of COVID-19. Ascorbic acid is a crucial vitamin necessary for the correct functioning of the immune system. It plays a role in stress response and has shown promising results when administered to the critically ill. Quercetin is a well-known flavonoid whose antiviral properties have been investigated in numerous studies. There is evidence that vitamin C and quercetin co-administration exerts a synergistic antiviral action due to overlapping antiviral and immunomodulatory properties and the capacity of ascorbate to recycle quercetin, increasing its efficacy. Safe, cheap interventions which have a sound biological rationale should be prioritized for experimental use in the current context of a global health pandemic. We present the current evidence for the use of vitamin C and quercetin both for prophylaxis in high-risk populations and for the treatment of COVID-19 patients as an adjunct to promising pharmacological agents such as Remdesivir or convalescent plasma.
Introduction
It is serendipitous (or perhaps indicative of hard work) that the Nobel prize winner Szent-Gyorgyi discovered both ascorbic acid (vitamin C) and the flavonoid quercetin (at the time labeled vitamin P) (1). Ascorbic acid is an essential vitamin with known antiviral properties (2) which is under investigation for its beneficial effects during the stress response in sepsis and critically ill patients (3).
Vitamin C exerts its antiviral properties by supporting lymphocyte activity, increasing interferon-α production, modulating cytokines, reducing inflammation, improving endothelial dysfunction, and restoring mitochondrial function (4–6). There are also suggestions that vitamin C may be directly viricidal (7). These in vitro effects, as we previously discussed (2), constitute a reflection of both the supra-physiological concentrations of ascorbate and the interaction between vitamin C and metal-containing culture media—both of which are pro-oxidant, generating reactive oxygen species.
Quercetin (also known as 3,3′,4′5,7-pentahydroxyflavone) is a widely distributed plant flavonoid, found in several vegetables, leaves, seeds, and grains, where it is conjugated with residual sugars to form quercetin glycosides (8). Studies suggest that quercetin supplementation may promote antioxidant (9), anti-inflammatory, antiviral (10), and immunoprotective effects (11). Quercetin has been studied in various types and models of viral infection due to its promising antiviral effects in inhibiting polymerases (12), proteases (13), reverse transcriptase (14), suppressing DNA gyrase, and binding viral capsid proteins (15, 16).
In this review we collate the evidence of the antiviral properties of quercetin, describe its biologic action and pharmacokinetics profile, expand on our previous review of vitamin C, discuss their synergistic actions, and propose this experimental multi-drug approach for the prevention and treatment of SARS-CoV-2/COVID-19 pandemic.
Conclusion
Quercetin displays a broad range of antiviral properties which can interfere at multiple steps of pathogen virulence -virus entry, virus replication, protein assembly- and that these therapeutic effects can be augmented by the co-administration of vitamin C. Furthermore, due to their lack of severe side effects and low-costs, we strongly suggest the combined administration of these two compounds for both the prophylaxis and the early treatment of respiratory tract infections, especially including COVID-19 patients.
