Role of zinc ionophores

Zinc ionophores can increase importation of zinc into cells. Increasing intracellular Zn⁺² concentration via zinc ionophores can efficiently impair intracellular replication of a variety of RNA viruses, including poliovirus, influenza virus and COVID-19-causing SARS-CoV-2 coronavirus, as demonstrated with such zinc ionophores as pyrrolidine dithiocarbamate and pyrithione. ²³

Zinc ionophores can thus be utilized to gain the anti-viral benefit of enhanced intracellular Zn⁺² concentrations while limiting tolerance/side-effect/toxicity issues ^24–26 associated with elevated serum levels of zinc supplementation. Another consideration for judicious selection of study zinc ionophore candidates included the compounds conferring additional benefits, particularly immunity health benefits.

Zinc ionophore activity has been shown in the alkaloid quinine ²⁷ and its chloroquine derivatives. ²⁸ For the study quinine-based zinc ionophore sourcing, we used Quina™ (NutraMedix; Jupiter, Florida USA), produced by a “proprietary [water: ethanol] extraction and enhancement process” from the bark of the quina plant Cinchona calisaya. There is no reason to believe that similar quina-bark-based extracts or derivatives would not serve as appropriate sourcing. We expect that extracts, tinctures or other preparations of quinine-containing plants, including but not limited to Quina Roja, can be adopted.

Quinine has also been shown to have an independent anti-viral activity against the COVID-19-causing SARS-CoV-2 coronavirus. ²⁹ Additionally, there is evidence of an anti-TNFα effect of quinine ³⁰ that may be contributory to the assumed protective anti-inflammatory effect for COVID-19 patients. For example, research on IBD patients relative to SARS-CoV-2 shows possible protective effects of anti-TNFα antibodies in Crohn’s patients. ³¹

Quercetin, a bioflavonoid polyphenol, has been shown to act as a zinc ionophore, ³² enhancing entrance of zinc into cells to inhibit viral intracellular replication. It is also believed to block viruses from entering cells in the first place. An Oak Ridge National Labs/University of Tennessee study of many FDA-approved compounds presented supercomputer modeling results for inhibition by them of SARS-CoV-2 viral S-spike binding to cells. The study ranked quercetin as fifth out of 20 top performers. ³³

Studies have shown quercetin also exhibiting anti-inflammatory properties, ^{34 –36} which could help mitigate the inflammatory response of cytokine and/or bradykinin storms provoked by COVID-19. A wide range of anti-viral/immunity benefits of quercetin have been identified, ^{37 –41} as well as other health benefits that may address some comorbidities of COVID-19 ^{42 –44} and some of its sequelae. ^44,45