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Influence of zinc deficiency and supplementation on NK cell cytotoxicity

Rolles et al., Journal of Functional Foods, doi:10.1016/j.jff.2018.07.027

Sep 2018

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Zinc for COVID-19

2nd treatment shown to reduce risk in July 2020

^*, now known with p = 0.0000013 from 44 studies, recognized in 11 countries.

Lower risk for mortality, ventilation, hospitalization, progression, recovery, and viral clearance.

No treatment is 100% effective. Protocols combine complementary and synergistic treatments. ^* >10% efficacy in meta analysis with ≥3 clinical studies.

4,100+ studies for 60+ treatments. c19early.org

In Vitro study showing improved natural killer (NK) cell function with zinc.

Graydon showed that a lower frequency of natural killer cells was associated with symptomatic COVID-19 infection.

9 preclinical studies support the efficacy of zinc for COVID-19:

4 In Silico studies Bess, El-Megharbel, Lockwood, Pormohammad

4 In Vitro studies El-Megharbel, Hajdrik, Panchariya, te Velthuis

1 In Vivo animal study El-Megharbel

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1. Bess et al., Identification of oral therapeutics using an AI platform against the virus responsible for COVID-19, SARS-CoV-2, Frontiers in Pharmacology, doi:10.3389/fphar.2023.1297924.frontiersin.org, doi.org.

2. El-Megharbel et al., Chemical and spectroscopic characterization of (Artemisinin/Quercetin/ Zinc) novel mixed ligand complex with assessment of its potent high antiviral activity against SARS-CoV-2 and antioxidant capacity against toxicity induced by acrylamide in male rats, PeerJ, doi:10.7717/peerj.15638.peerj.com, doi.org.

3. Graydon et al., High baseline frequencies of natural killer cells are associated with asymptomatic SARS-CoV-2 infection, Current Research in Immunology, doi:10.1016/j.crimmu.2023.100064.sciencedirect.com, doi.org.

4. Hajdrik et al., In Vitro Determination of Inhibitory Effects of Humic Substances Complexing Zn and Se on SARS-CoV-2 Virus Replication, Foods, doi:10.3390/foods11050694.mdpi.com, doi.org.

5. Lockwood, T., Coordination chemistry suggests that independently observed benefits of metformin and Zn2+ against COVID-19 are not independent, BioMetals, doi:10.1007/s10534-024-00590-5.springer.com, doi.org.

6. Panchariya et al., Zinc2+ ion inhibits SARS-CoV-2 main protease and viral replication in vitro, Chemical Communications, doi:10.1039/D1CC03563K.rsc.org, doi.org.

7. Pormohammad et al., Zinc and SARS-CoV-2: A molecular modeling study of Zn interactions with RNA-dependent RNA-polymerase and 3C-like proteinase enzymes, International Journal of Molecular Medicine, doi:10.3892/ijmm.2020.4790.spandidos-publications.com, doi.org.

8. te Velthuis et al., Zn2+ Inhibits Coronavirus and Arterivirus RNA Polymerase Activity In Vitro and Zinc Ionophores Block the Replication of These Viruses in Cell Culture, PLOS Pathogens 2010, 6:11, doi:10.1371/journal.ppat.1001176.plos.org, doi.org.

Rolles et al., 30 Sep 2018, peer-reviewed, 3 authors. Contact: lrink@ukaachen.de.

In Vitro studies are an important part of preclinical research, however results may be very different in vivo.

This Paper Zinc All

Influence of zinc deficiency and supplementation on NK cell cytotoxicity

Benjamin Rolles, Martina Maywald, Lothar Rink

Journal of Functional Foods, doi:10.1016/j.jff.2018.07.027

Knowledge about the role of zinc on natural killer (NK) cell activity and function is limited and needs further instigation. Hence, in this study, the influence of interleukin (IL)-1, IL-2, zinc, and the zinc-chelator N,N,N′,N′tetrakis(2-pyridylmethyl)ethane-1,2-diamine (TPEN) on the human NK cell line (YTS cell line) and primary NK cells were examined. We mainly focused on NK cell killing activity by using the K562 cell line as target cells. We uncovered a significantly increased NK cell killing activity due to 1 h zinc pre-incubation and contact to zinc-rich medium in physiological concentrations. Moreover, co-stimulation of zinc and IL-2 provoked an additive increase in NK cell killing activity. In contrast, zinc deficiency induced by 1 h TPEN pre-incubation significantly decreased the killing activity of primary NK cells. Temporary elevated intracellular zinc levels in target cells act contrary to the destruction by NK cells.

Conflict of Interests The authors declare no conflict of interest.

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