Zinc Ionophore Activity of Quercitin and EGCG

As ways to boost immunity and protect against infection continue to be front and center issues in our world, research focused on nutritional support for the immune system continues to progress.

Zinc has become a major topic of interest of late, since this tried-and-true mineral has been in the news for its ability to prevent viral replication and its role in regulating the inflammasome response that leads to cytokine storms.  

Zinc alone is effective depending on the form.  Not all zincs are created equal, however, and forms such as glycinate and arginate appear to be the most bioavailable.  That said, there may be ways to enhance the bioavailability of zinc, thus providing an even greater impact on immunity and viral load.

Getting zinc into the cell is obviously dependent on having adequate levels of zinc outside the cell. With most of us, this is usually not a problem. However, zinc absorption does vary by individual. Physiological stressors, such as infection and inflammation, tend to deplete zinc pretty fast.

Zinc is a decidedly anti-viral mineral. High intracellular concentrations inhibit the replication of RNA type viruses, such as SARS-CoV-2. Zinc does this by blocking RNA-dependent RNA polymerase (RdRp), the core enzyme of the multiprotein replication and transcription complex critical for the copying of viral RNA. 

That’s the conundrum. In high concentrations, zinc can block coronavirus reproduction, but the cell typically does not tolerate high levels of zinc due to its other actions.

Enter the zinc ionophores.

An ionophore is any substance which is able to transport particular ions across a lipid membrane in a cell. In the case of zinc, there are molecules that can act as facilitators and enhance the entry of zinc into the cell. These are known as zinc ionophores. 

Quercetin and EGCG from green tea are zinc ionophores.  These plant polyphenols  act as antioxidants and as signaling molecules.1

Quercetin plus zinc is being tested as an antiviral in human clinical trials for the treatment of Covid-19. The combination had already made it through animal trials for use against Ebola and SARS-CoV1, and was approved by the FDA for human clinical trials. Plans are underway for a large scale trial in China for patients with Covid-19.

Using these compounds in combination can be a very powerful option against viral infections.  

1. Zinc inophore Activity of Quercetin and Epigallocatechin gallate: From Hepa 1-6 Cells to Liposome Model, July 2014, Journal of Agriculture and Food Chemistry, 62(32), PubMed)