Zinc Studies-p53, MDM2
zinc protect,reactivate p53 and increase chemosensitivity.
zinc chelators have counter effect of zinc.
Whereas starving p53 of zinc by chelation or tumorigenic mutation (e.g. R175H) can induce structural changes, too much zinc can do the same.
p53 can sensitize cancer cells to ascorbate via ROS.
Zinc metallochaperones (ZMC) are a new class of mutant p53 reactivators that restore WT structure and function to zinc-deficient p53 mutants.
quercetin and EGCG from green tea, are zinc ionophores. Quercetin also inhibits replication of coronavirus.
The murine double minute 2 (MDM2) protein is overexpressed in a number of human malignancies, including pancreatic cancer.
PTEN (phosphatase and tensin homologue deleted on chromosome 10) phosphatase is the major antagonist of the AKT pathway, it follows that PTEN protects p53 from degradation by inhibiting PI3K and is therefore an important component of the p53 stress response.
DHA increases PTEN
zinc transporter and zinc import proteins：zinc8
zinc for diabetes: beta cells have highest concentration of zinc, improve function, antioxidant, blood sugar control, prevention,
https://www.frontiersin.org/articles/10.3389/fonc.2020.00646/full
A carbonic anhydrase, or carbonate dehydratase, is a type of enzyme that rapidly catalyzes the conversion of carbon dioxide into a proton and the bicarbonate ion (HCO3-). This reaction is rather slow in the absence of the anhydrase catalyst, as the reaction with the enzyme takes place typically ten thousand to one million (10^4-10^6) times per second. The active site by which the enzyme binds contains a zinc ion (Zn2+), by which t…
https://en.wikibooks.org/wiki/Structural_Biochemistry/Enzyme_Catalytic_Mechanism/Carbonic_Anhydrase
The key target of Mdm2 is the p53 tumor suppressor. Mdm2 has been identified as a p53 interacting protein that represses p53 transcriptional activity. Mdm2 achieves this repression by binding to and blocking the N-terminal trans-activation domain of p53. Mdm2 is a p53 responsive gene—that is, its transcription can be activated by p53. Thus when p53 is stabilized, the transcription of Mdm2 is also induced, resulting in higher Mdm2 protein levels.
Mdm2 - Wikipedia
https://en.wikipedia.org/wiki/Mdm2Escape, or Vanish: Control the Fate of p53 through MDM2-Mediated Ubiquitination
p53 protein is a prominent tumor suppressor to induce cell cycle arrest, apoptosis and senescence, which attracts significant interest to cancer treatment. Therefore, it would be particularly important to restore the wild–type p53 that retains latent functions in the approximately 50% of tumors. MDM2 (murine double minute 2), the principal cellular antagonist of p53, has long been believed to suppress p53 activity through two main mechanisms: promoting degradation via its E3 ligase activity and masking p53 transcriptional activation by direct binding. Targeting MDM2 E3 ligase activity is becoming a potential antitumor strategy resulting from MDM2’s decisive role in controlling the fate of p53: p53 is going to degradation when entrapped into MDM2-mediated ubiquitination, where p53 can escape by abrogating MDM2 E3 ligase activity using regulators. The intensive focus on regulating MDM2 ubiquitin E3 ligase activity has led to the rapid progress of its inhibitors, which may be possible to help p53 escape from degradation and restore its function to control tumor growth. This review summarizes the current inhibitors of MDM2 E3 ligase in cancer therapy based on the understanding the regulation of MDM2 E3 ubiquitin ligase activity, including post-translational modification, interactions between MDM2 and its cofactors, and regulation of MDM2 stability.
Keywords: Antitumor strategy, degradation, E3 ligase activity, MDM2, p53, ubiquitination.Escape, or Vanish: Control the Fate of p53 through MDM2-Mediated Ubiquitination | Bentham Science
https://www.eurekaselect.com/134710/article?tracking-code=4
http://www.biologyexams4u.com/2013/08/p53-and-mdm2-interaction-how-p53.html
Med Hypotheses. 1999 Jul;53(1):6-16.
Modern diets and diseases: NO-zinc balance. Under Th1, zinc and nitrogen monoxide (NO) collectively protect against viruses, AIDS, autoimmunity, diabetes, allergies, asthma, infectious diseases, atherosclerosis and cancer.
Sprietsma JE1.
Abstract
Thanks to progress in zinc research, it is now possible to describe in more detail how zinc ions (Zn++) and nitrogen monoxide (NO), together with glutathione (GSH) and its oxidized form, GSSG, help to regulate immune responses to antigens. NO appears to be able to liberate Zn++ from metallothionein (MT), an intracellular storage molecule for metal ions such as zinc (Zn++) and copper (Cu++). Both Zn++ and Cu++ show a concentration-dependent inactivation of a protease essential for the proliferation of the AIDS virus HIV-1, while zinc can help prevent diabetes complications through its intracellular activation of the enzyme sorbitol dehydrogenase (SDH). A Zn++ deficiency can lead to a premature transition from efficient Th1-dependent cellular antiviral immune functions to Th2-dependent humoral immune functions. Deficiencies of Zn++, NO and/or GSH shift the Th1/Th2 balance towards Th2, as do deficiencies of any of the essential nutrients (ENs) - a group that includes methionine, cysteine, arginine, vitamins A, B, C and E, zinc and selenium (Se) - because these are necessary for the synthesis and maintenance of sufficient amounts of GSH, MT and NO. Via the Th1/Th2 balance, Zn++, NO, MT and GSH collectively determine the progress and outcome of many diseases. Disregulation of the Th1/Th2 balance is responsible for autoimmune disorders such as diabetes mellitus. Under Th2, levels of interleukin-4 (II-4), II-6, II-10, leukotriene B4 (LTB4) and prostaglandin E2 (PGE2) are raised, while levels of II-2, Zn++, NO and other substances are lowered. This makes things easier for viruses like HIV-1 which multiply in Th2 cells but rarely, if ever, in Th1 cells. AIDS viruses (HIVs) enter immune cells with the aid of the CD4 cell surface receptor in combination with a number of co-receptors which include CCR3, CCR5 and CXCR4. Remarkably, the cell surface receptor for LTB4 (BLTR) also seems to act as a co-receptor for CD4, which helps HIVs to infect immune cells. The Th2 cytokine II-4 increases the number of CXCR4 and BLTR co-receptors, as a result of which, under Th2, the HIV strains that infect immune cells are precisely those that are best able to accelerate the AIDS disease process. The II-4 released under Th2 therefore not only promotes the production of more HIVs and the rate at which they infect immune cells, it also stimulates selection for the more virulent strains. Zn++ inhibit LTB4 production and numbers of LTB4 receptors (BLTRs) in a concentration-dependent way. Zn++ help cells to keep their LTB4 'doors' shut against the more virulent strains of HIV. Moreover, a sufficiency of Zn++ and NO prevents a shift of the Th1/Th2 balance towards Th2 and thereby slows the proliferation of HIV, which it also does by inactivating the HIV protease. Research makes it look likely that deficiencies of ENs such as zinc promote the proliferation of Th2 cells at the expense of Th1 cells. Zinc deficiency also promotes cancer. Under the influence of Th1 cells, zinc inhibits the growth of tumours by activating the endogenous tumour-suppressor endostatin, which inhibits angiogenesis. The modern Western diet, with its excess of refined products such as sugar, alcohol and fats, often contains, per calorie, a deficiency of ENs such as zinc, selenium and vitamins A, B, C and E, which results in disturbed immune functions, a shifted Th1/Th2 balance, chronic (viral) infections, obesity, atherosclerosis, autoimmunity, allergies and cancer. In view of this, an optimization of dietary composition would seem to give the best chance of beating (viral) epidemics and common (chronic) diseases at a realistic price.
PMID: 10499817 DOI: 10.1054/mehy.1999.0867
[Indexed for MEDLINE]Modern diets and diseases: NO-zinc balance. Under Th1, zinc and nitrogen monoxide (NO) collectively protect against viruses, AIDS, autoimmunity, di... - PubMed - NCBI
https://www.ncbi.nlm.nih.gov/pubmed/10499817
FOR MELANOMA
Zinc induces apoptosis by increasing ROS levels and via modulation of p53 and FAS/FAS ligand (FASL) protein expression in WM 266-4 cells. p53 regulates the intracellular redox state and induces ROS-dependent apoptosis (180). Zinc oxide nanoparticles known to possess semiconductor properties induce oxidative stress, enhance ROS production and deplete GSH in A375 cells. These particles induce genotoxic and apoptotic response via caspase 3-dependent mechanism (181). ZnO nanoparticles also induce oxidative stress in Cloudman S91 melanoma cancer cells. Exposure to these nanoparticles leads to a spontaneous increase in the ROS levels and membrane lipid peroxidation along with a decrease in the level of GSH, SOD and catalase (182).
cancer-research-frontiers.org/2018-4-101/
http://cancer-research-frontiers.org/2018-4-101/
Adv Nutr. 2013 Mar; 4(2): 176–190.
Discovery of Human Zinc Deficiency: Its Impact on Human Health and Disease1,2,3
Ananda S. Prasad*
锌对健康的重要性在1963年首次被证实。
估计发展中国家有20亿人缺锌-主要是高植酸蛋白的摄入而非动物性蛋白。
缺锌在在慢性消化不良、肝脏疾病、慢性肾病和其他慢性疾病中非常普遍。
在中东地区，缺锌的儿童活不到25岁，通常是死于反复的感染。
1963年，只知道3种的含锌酶，至今，已发现的含锌酶超过300种，另外，超过1000个转录因子需要锌。
锌是细胞内的第二信使，参与细胞信号的转送。
锌治疗腹泻、普通感冒和预防失明的效果显著。因此，世卫组织要求成员国把补锌作为治疗腹泻的一线治疗。
锌还是一种抗氧化剂和抗炎因子。
Abstract
The essentiality of zinc in humans was established in 1963. During the past 50 y, tremendous advances in both clinical and basic sciences of zinc metabolism in humans have been observed. The major factor contributing to zinc deficiency is high phytate-containing cereal protein intake in the developing world, and nearly 2 billion subjects may be zinc deficient. Conditioned deficiency of zinc has been observed in patients with malabsorption syndrome, liver disease, chronic renal disease, sickle cell disease, and other chronic illnesses. Major clinical problems resulting from zinc deficiency in humans include growth retardation; cell-mediated immune dysfunction, and cognitive impairment. In the Middle East, zinc-deficient dwarfs did not live beyond the age of 25 y, and they died because of intercurrent infections. In 1963, we knew of only 3 enzymes that required zinc for their activities, but now we know of >300 enzymes and >1000 transcription factors that are known to require zinc for their activities. Zinc is a second messenger of immune cells, and intracellular free zinc in these cells participate in signaling events. Zinc has been very successfully used as a therapeutic modality for the management of acute diarrhea in children, Wilson’s disease, the common cold and for the prevention of blindness in patients with age-related dry type of macular degeneration and is very effective in decreasing the incidence of infection in the elderly. Zinc not only modulates cell-mediated immunity but is also an antioxidant and anti-inflammatory agent.Discovery of Human Zinc Deficiency: Its Impact on Human Health and Disease
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3649098/
Cell Cycle. 2011 May 15;
Restoring p53 Active Conformation by Zinc Increases the Response of Mutant p53 Tumor Cells to Anticancer Drugs
Rosa Puca 1, Lavinia Nardinocchi, Manuela Porru, Amos J Simon, Gideon Rechavi, Carlo Leonetti, David Givol, Gabriella D'Orazi
1National Cancer Institute Regina Elena, Rome, Italy.
Absence of p53 expression or expression of mutant p53 (mtp53) are common in human cancers and are associated with increased cancer resistance to chemo- and radiotherapy. Therefore, significant efforts towards pharmaceutical reactivation of defective p53 pathways are underway. We previously reported that, in HIPK2 knockdown background, p53 undergoes misfolding with inhibition of DNA binding and transcriptional activities that correlate with increased chemoresistance, and that zinc rescues wild-type p53 activity. Zinc has a crucial role in the biology of p53, in that p53 binds to DNA through a structurally complex domain stabilized by zinc atom. In this study, we explored the role of zinc in p53 reactivation in mutant p53-expressing cancer cells. We found that zinc re-established chemosensitivity in breast cancer SKBR3 (expressing R175H mutation) and glioblastoma U373MG (expressing R273H mutation) cell lines. Biochemical studies showed that zinc partly induced the transition of mutant p53 protein (reactive to conformation-sensitive PAb240 antibody for mutant conformation) into a functional conformation (reactive to conformation-sensitive PAb1620 antibody for wild-type conformation). Zinc-mediated p53 reactivation also reduced the mtp53/p73 interaction restoring both wtp53 and p73 binding to target gene promoters by ChIP assay with in vivo induction of wtp53 target gene expression, which rendered mutant p53 cells more prone to drug killing in vitro. Finally, zinc administration in U373MG tumor xenografts increased drug-induced tumor regression in vivo, which correlated with increased wild-type p53 protein conformation. These results show that the use of zinc might restore drug sensitivity and inhibit tumor growth by reactivating mutant p53.Restoring p53 Active Conformation by Zinc Increases the Response of Mutant p53 Tumor Cells to Anticancer Drugs - PubMed
https://pubmed.ncbi.nlm.nih.gov/21508668/
Free Radical Biology and Medicine
Volume 53, Issue 8, 15 October 2012,
Enhanced antitumor activity of vitamin C via p53 in Cancer cells
JinsunKimaSoon-DuckLeeaBoogiChangaDong-HoonJinbSam-IlJungaMee-YoungParkaYoungsooHanaYoungYangaKeunIl KimaJong-SeokLimaYoung-SookKangcMyeong-SokLeea
Ascorbate is an important natural antioxidant that can selectively kill cancer cells at pharmacological concentrations. Despite its benefit, it is quite difficult to predict the antitumor effects of ascorbate, because the relative cytotoxicity of ascorbate differs between cancer cell lines. Therefore, it is essential to examine the basis for this fundamental disagreement. Because p53 is activated by DNA-damaging stress and then regulates various cellular conditions, we hypothesized that p53 can sensitize cancer cells to ascorbate. Using isogenic cancer cells, we observed that the presence of p53 can affect ascorbate cytotoxicity, and also reactivation of p53 can make cancer cells sensitive to ascorbate. p53-dependent enhancement of ascorbate cytotoxicity is caused by increased reactive oxygen species generation via a differentially regulated p53 transcriptional network. We also found that transcriptionally activated p53 was derived from MDM2 ubiquitination by ascorbate and subsequently its signaling network renders cancer cells more susceptible to oxidative stress. Similar to the p53 effect on in vitro ascorbate cytotoxicity, inhibition of tumor growth is also stronger in p53-expressing tumors than in p53-deficient ones in vivo. This is the first observation that ascorbate cytotoxicity is positively related to p53 expression, activating its transcriptional network to worsen intracellular oxidative stress and consequently enhancing its cytotoxicity. Based on our study, reactivation of p53 may help to achieve more consistent cytotoxic effects of ascorbate in cancer therapies.
Highlights
► One of the reasons for differing ascorbate cytotoxicity may be the presence of p53. ► The modification of p53 expression changed ascorbate cytotoxicity. ► Ascorbate overcame the threshold level of oxidative stress, causing cell death via p53. ► p53 and MDM2 are differentially regulated by ascorbate. ► In vivo antitumor activity is enhanced by the presence of p53.Enhanced antitumor activity of vitamin C via p53 in Cancer cells - ScienceDirect
https://www.sciencedirect.com/science/article/abs/pii/S089158491200473X
Journal of Experimental & Clinical Cancer Research, Published: 07 October 2013 A fluorescent curcumin-based Zn(II)-complex reactivates mutant (R175H and R273H) p53 in cancer cells Alessia Garufi, Daniela Trisciuoglio, Manuela Porru, Carlo Leonetti, Antonella Stoppacciaro, Valerio D’Orazi, Maria Laura Avantaggiati, Alessandra Crispini, Daniela Pucci & Gabriella D’Orazi Abstract Background Mutations of the p53 oncosuppressor gene are amongst the most frequent aberration seen in human cancer. Some mutant (mt) p53 proteins are prone to loss of Zn(II) ion that is bound to the wild-type (wt) core, promoting protein aggregation and therefore unfolding. Misfolded p53 protein conformation impairs wtp53-DNA binding and transactivation activities, favouring tumor growth and resistance to antitumor therapies. Screening studies, devoted to identify small molecules that reactivate mtp53, represent therefore an attractive anti-cancer therapeutic strategy. Here we tested a novel fluorescent curcumin-based Zn(II)-complex (Zn-curc) to evaluate its effect on mtp53 reactivation in cancer cells. Methods P53 protein conformation was examined after Zn-curc treatment by immunoprecipitation and immunofluorescence assays, using conformation-specific antibodies. The mtp53 reactivation was evaluated by chromatin-immunoprecipitation (ChIP) and semi-quantitative RT-PCR analyses of wild-type p53 target genes. The intratumoral Zn-curc localization was evaluated by immunofluorescence analysis of glioblastoma tissues of an ortothopic mice model. Results The Zn-curc complex induced conformational change in p53-R175H and -R273H mutant proteins, two of the most common p53 mutations. Zn-curc treatment restored wtp53-DNA binding and transactivation functions and induced apoptotic cell death. In vivo studies showed that the Zn-curc complex reached glioblastoma tissues of an ortothopic mice model, highlighting its ability to crossed the blood-tumor barrier. Conclusions Our results demonstrate that Zn-curc complex may reactivate specific mtp53 proteins and that may cross the blood-tumor barrier, becoming a promising compound for the development of drugs to halt tumor growth.
A fluorescent curcumin-based Zn(II)-complex reactivates mutant (R175H and R273H) p53 in cancer cells | Journal of Experimental & Clinical Cancer Research | Full Text
https://jeccr.biomedcentral.com/articles/10.1186/1756-9966-32-72
The antiviral role of zinc and metallothioneins in ...
https://www.ncbi.nlm.nih.gov/pubmed/29239069
Metallothioneins (MTs) are small, cysteine-rich proteins characterized by a high affinity for monovalent and divalent cations, such as copper and zinc. Of the four known MT isoforms, only, members of the MT 1 and 2 subfamilies are widely expressed, acting as metal chaperones whose primary role is to mediate intracellular zinc homoeostasis.
Cited by: 6
Publish Year: 2018
Author: S. A. Read, G. Parnell, D. Booth, M. W. Douglas,
Zinc vs HCV: Researchers confirm inflammatory, antiviral ...
https://www.mdlinx.com/infectious-disease/article/1458
Feb 22, 2018 · Finally, Dr. Read and colleagues found that the antiviral effect of zinc against HCV was mediated through the induction of MTs (P < 0.05). “The data highlight the potential for zinc to be used as a simple and effective treatment against acute and chronic inflammation in …
The Role of Zinc in Antiviral Immunity.
https://www.ncbi.nlm.nih.gov/pubmed/31305906
Jul 01, 2019 · This review summarizes current basic science and clinical evidence examining zinc as a direct antiviral, as well as a stimulant of antiviral immunity. An abundance of evidence has accumulated over the past 50 y to demonstrate the antiviral activity of zinc against a variety of viruses, and via numerous mechanisms.
Cited by: 2
Publish Year: 2019
Author: Scott A Read, Stephanie Obeid, Chantelle Ahlenstiel, Golo Ahlenstiel
TRIM25 Is Required for the Antiviral Activity of Zinc ...
https://www.ncbi.nlm.nih.gov/pubmed/28202764
Apr 13, 2017 · TRIM25 Is Required for the Antiviral Activity of Zinc Finger Antiviral Protein. Zheng X(1)(2), Wang X(1), Tu F(1), Wang Q(1), Fan Z(1), Gao G(3). Author information: (1)CAS Key Laboratory of Infection and Immunity, Institute of Biophysics, Chinese Academy of Sciences, Beijing, China. (2)University of Chinese Academy of Sciences, Beijing, China.
Cited by: 23
Publish Year: 2017
Author: Xiaojiao Zheng, Xinlu Wang, Fan Tu, Qin Wang, Zusen Fan, Guangxia Gao
Antiviral activity of zinc salts against transmissible ...
https://www.sciencedirect.com/science/article/pii/S0378113512003719
Zinc has been shown to mediate antiviral effects against certain viruses. However, the underlying mechanisms are still largely unknown. We investigated the effects of the two zinc salts, zinc chloride (ZnCl 2 ) and zinc sulfate (ZnSO 4 ), on infection of swine testicle (ST) cells with transmissible gastroenteritis virus (TGEV) and compared it to the effects of a control salt, magnesium sulfate …
Cited by: 12
Publish Year: 2012
Author: Zhanyong Wei, Zhanyong Wei, Michael Burwinkel, Christiane P
The Zinc-Finger Antiviral Protein ZAP Inhibits LINE and ...
journals.plos.org/plosgenetics/article?id=10.1371/journal.pgen.1005121
Here, we demonstrate that the zinc-finger antiviral protein (ZAP) inhibits the retrotransposition of human L1 and Alu retrotransposons, as well as related retrotransposons from mice and zebrafish. Biochemical and genetic data suggest that ZAP interacts with L1 RNA.
CCCH‐type zinc finger antiviral protein mediates antiviral ...
https://jlb.onlinelibrary.wiley.com/doi/abs/10.1002/JLB.1AB1119-314RRR
The zinc finger antiviral protein (ZAP), as a host restriction factor, inhibits the replication of certain viruses by binding viral mRNA or proteins for degradation. However, little is known about the role of ZAP in the antiviral immune response.
Author: Mingjun Zhu, Jing Zhou, Yanfei Liang, Venugopal Nair, Yongxiu Yao, Ziqiang Cheng
Publish Year: 2020
Molecular Mechanism of RNA Recognition by Zinc-Finger ...
https://www.sciencedirect.com/science/article/pii/S2211124719316390
Zinc-finger antiviral protein (ZAP) is a host antiviral factor that specifically restricts a wide range of viruses. ZAP selectively binds to CG-dinucleotide-enriched RNA sequences and recruits multiple RNA degradation machines to degrade target viral RNA.
Author: Xiu Luo, Xiu Luo, Xinlu Wang, Yina Gao, Jingpeng Zhu, Songqing Liu, Guangxia Gao, Pu Gao
Publish Year: 2020
Zinc-finger antiviral protein inhibits HIV-1 infection by ...
https://www.pnas.org/content/108/38/15834
Sep 20, 2011 · The zinc-finger antiviral protein (ZAP) was originally identified as a host factor that inhibits the replication of Moloney murine leukemia virus. Here we report that ZAP inhibits HIV-1 infection by promoting the degradation of specific viral mRNAs.
Cited by: 157
Publish Year: 2011
Author: Yiping Zhu, Guifang Chen, Fengxiang Lv, Xinlu Wan
Inhibition of H1N1 influenza virus infection by zinc oxide ...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6734352
Sep 10, 2019 · Inhibition of H1N1 influenza virus infection by zinc oxide nanoparticles: another emerging application of nanomedicine Hadi Ghaffari , 1 Ahmad Tavakoli , 1 Abdolvahab Moradi , 2 Alijan Tabarraei , 2 Farah Bokharaei-Salim , 1 Masoumeh Zahmatkeshan , 3, 4 Mohammad Farahmand , 5 Davod Javanmard , 1 Seyed Jalal Kiani , 1 Maryam Esghaei , 1 Vahid Pirhajati-Mahabadi , 3, 6 Angila Ataei …
Cited by: 1
Publish Year: 2019
Author: Hadi Ghaffari, Ahmad Tavakoli, Abdolvahab Moradi, Alijan Tabarraei, Farah Bokharaei-Salim, Masoumeh ...
In vivo anti-influenza virus activity of a zinc finger ...
https://www.ncbi.nlm.nih.gov/pubmed/9056014
In vivo anti-influenza virus activity of a zinc finger peptide. Judd AK(1), Sanchez A, Bucher DJ, Huffman JH, Bailey K, Sidwell RW. Author information: (1)SynVax, Belmont, California 94002, USA. Matrix protein (M1) is a major structural protein of influenza virus, and it inhibits its own polymerase.
Cited by: 21
Publish Year: 1997
Author: A K Judd, A Sanchez, D J Bucher, J H Huffman, K Bailey, R W Sidwell
Inhibition of H1N1 influenza virus infection by zinc oxide ...
https://jbiomedsci.biomedcentral.com/articles/10.1186/s12929-019-0563-4
Sep 10, 2019 · Currently available anti-influenza drugs are often associated with limitations such as toxicity and the appearance of drug-resistant strains. Therefore, there is a pressing need for the development of novel, safe and more efficient antiviral agents. In this study, we evaluated the antiviral activity of zinc oxide nanoparticles (ZnO-NPs) and PEGylated zinc oxide nanoparticles against H1N1 ...
Cited by: 1
Publish Year: 2019
Author: Hadi Ghaffari, Ahmad Tavakoli, Abdolvahab Moradi, Alijan Tabarraei, Farah Bokharaei-Salim, Masoumeh ...
Author: Hadi Ghaffari
The combination of chloroquine with zinc enhanced chloroquine's cytotoxicity and induced apoptosis in A2780 cells. Thus chloroquine is a zinc ionophore, a property that may contribute to chloroquine's anticancer activity.
(PDF) Chloroquine Is a Zinc Ionophore - ResearchGate
www.researchgate.net/publication/266380650_Chloroquine_Is_a_Zinc_Ionophore
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Chloroquine Is a Zinc Ionophore - PubMed Central (PMC)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4182877
Oct 01, 2014 · Clioquinol, an established zinc ionophore that targets zinc to lysosomes , was used as a positive control (Figure 4B). Thus, chloroquine is a zinc ionophore that targets zinc to cellular lysosomes.
Cited by: 5
Publish Year: 2014
Author: Jing Xue, Jing Xue, Amanda Moyer, Bing Peng, Bing Peng, Jinchang Wu, Bethany N. Hannafon, Wei Qun Di...
Chloroquine is a zinc ionophore.
https://www.ncbi.nlm.nih.gov/pubmed/25271834
Oct 01, 2014 · The combination of chloroquine with zinc enhanced chloroquine's cytotoxicity and induced apoptosis in A2780 cells. Thus chloroquine is a zinc ionophore, a property that may contribute to chloroquine's anticancer activity.
Cited by: 5
Publish Year: 2014
Author: Jing Xue, Jing Xue, Amanda Moyer, Bing Peng, Bing Peng, Jinchang Wu, Bethany N. Hannafon, Wei Qun Di...
(PDF) Chloroquine Is a Zinc Ionophore - ResearchGate
https://www.researchgate.net/publication/266380650...
The combination of chloroquine with zinc enhanced chloroquine's cytotoxicity and induced apoptosis in A2780 cells. Thus chloroquine is a zinc ionophore, a property that may contribute to chloroquine's anticancer activity.
Modern Medicine Knew of the Zinc Cure for Coronavirus ...
https://www.lewrockwell.com/2020/04/bill-sardi/...
Apr 07, 2020 · Further investigation finds that quercetin, found naturally in red apples and red onions, is a zinc ionophore. Quercetin is widely available in health shops, and represents a “poor man’s chloroquine.” Quercetin also inhibits replication of coronavirus. Ineffective synthetic drugs and vaccines or economical zinc?
Covid-19: Chloroquine, Zinc and Quercetin – People, Nature ...
https://dadamo.com/dangerous/2020/04/07/covid-19...
Apr 07, 2020 · In addition to chloroquine, the nutraceuticals quercetin (bioflavonoid) and epigallocatechin-gallate (green tea polyphenol) are also zinc ionophores. Quercetin plus zinc is being tested as an anti-viral in human clinical trials for the treatment of Covid-19.
Is a combo of chloroquine and Zinc a cure for coronavirus?
https://www.researchgate.net/post/Is_a_combo_of...
It so happens that chloroquine is a zinc ionophore, thus provides zinc++ with the transport mechanism.
Chloroquine, Zinc Tested to Block COVID Infection
https://www.webmd.com/lung/news/20200409/...
Apr 09, 2020 · Chloroquine, Zinc Tested to Block COVID Infection. By Karen Weintraub. April 9, 2020 -- In the United States and Europe, a handful of clinical trials have begun to test ways to keep health care ...
Chloroquine and Natural Solutions for Coronavirus | Dr ...
drdahlman.com/chloroquine-and-natural-solutions-for-coronavirus
It is well known that chloroquine (anti-malarial drug) is a zinc ionophore. This study examines this concept (from October 1, 2014): Chloroquine is a Zinc Ionophore The above study was not related to COVID-19, but found that they were able to detect additional zinc inside the cell when using chloroquine.
Chloroquine, Zinc & COVID-19 - My Quin Story
www.myquinstory.info/chloroquine-zinc-covid-19
Chloroquine, despite its toxicity, is a Zinc ionophore, in an of itself. The greater the concentration of Chloroquine in the cell, the great amount of zinc (as seen in the chart to the right).
Structural basis for inhibition of the RNA-dependent RNA ...
https://science.sciencemag.org/content/early/2020/04/30/science.abc1560
Apr 30, 2020 · The pandemic of Corona Virus Disease 2019 (COVID-19) caused by SARS-CoV-2 has become a global crisis. The replication of SARS-CoV-2 requires the viral RNA-dependent RNA polymerase (RdRp), a target of the antiviral drug, Remdesivir. Here we report the cryo-EM structure of the SARS-CoV-2 RdRp either in the apo form at 2.8 Å resolution or in complex with a 50-base template-primer RNA and ...
Zn2+ Inhibits Coronavirus and Arterivirus RNA Polymerase ...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2973827
Nov 04, 2010 · The RNA synthesis of these two distantly related nidoviruses is catalyzed by an RNA-dependent RNA polymerase (RdRp), which is the core enzyme of their multiprotein replication and transcription complex (RTC).
The antiviral compound remdesivir potently inhibits RNA ...
https://www.jbc.org/content/early/2020/02/24/jbc.AC120.013056
Remdesivir (RDV) is an investigational compound with a broad spectrum of antiviral activities against RNA viruses, including SARS-CoV and Middle East respiratory syndrome (MERS-CoV). RDV is a nucleotide analog inhibitor of RNA-dependent RNA polymerases (RdRps).
Cited by: 5
Publish Year: 2020
Author: Calvin J Gordon, Egor P Tchesnokov, Joy Y. Feng, Danielle P Porter, Matthias Gotte
Zn(2+) inhibits coronavirus and arterivirus RNA polymerase ...
https://www.ncbi.nlm.nih.gov/pubmed/21079686
Nov 04, 2010 · The RNA synthesis of these two distantly related nidoviruses is catalyzed by an RNA-dependent RNA polymerase (RdRp), which is the core enzyme of their multiprotein replication and transcription complex (RTC).
Cited by: 40
Publish Year: 2010
Author: Aartjan J. W. te Velthuis, Sjoerd H. E. van den Worm, Amy C. Sims, Ralph S. Baric, Eric J. Snijder, ...
Mechanism of action revealed for remdesivir, potential ...
https://www.drugtargetreview.com/news/56798/...
Mar 03, 2020 · They found that remdesivir blocks a particular enzyme that is required for viral replication. Coronaviruses replicate by copying their genetic material using an enzyme known as the RNA-dependent RNA polymerase. Until now, it has been difficult to get the polymerase complex that contains multiple proteins to work in a test tube.
The potential chemical structure of anti‐SARS‐CoV‐2 RNA ...
https://onlinelibrary.wiley.com/doi/full/10.1002/jmv.25761
Remdesivir (GS‐5734) is a 1′‐cyano‐substituted adenosine nucleotide analog inhibitor of RdRp and shows broad‐spectrum antiviral activity against several RNA viruses, including Ebola virus, SARS‐CoV, and MERS‐CoV. 3-5 More importantly, one report indicated that remdesivir improved the critical condition of one COVID‐19 patient. 6 Therefore, RdRp could be an attractive therapeutic target for SARS‐CoV‐2.
Author: Jrhau Lung, Yu‐Shih Lin, Yao‐Hsu Yang, Yao‐Hsu Yang, Yu‐Lun Chou, Li‐Hsin Shu, Yu‐Ching Cheng, Hung ...
Publish Year: 2020
添加锌：从对抗冠状病毒的游戏改变者到游戏获胜者
JP伦纳德，4月16日
我们能否相信SARS-CoV-2的肯定治愈报告？
这是羟氯喹加锌的科学依据
另请参阅简短主题：如何以及现在和当前项目如何阻止病毒和隔离区：FieldTrials.net
这场噩梦唯一的幸福结局就是病毒被迅速治愈。一种治疗方法被隐瞒了吗?
3月23日，脱口秀主持人肖恩·汉尼提(Sean Hannity)在节目中打电话给副总统迈克·彭斯(Mike Pence)，谈论弗拉基米尔·泽连科医生(Vladimir Zelenko)的羟氯喹、阿奇霉素和锌组成的“神奇药物”。“他的结果是:我们有零死亡，零住院，零插管，零。”
彭斯回应说，“我们在一些轶事研究中看到的，我们将进行测试，”然后继续谈论羟氯喹和疫苗。“锌”落在盲点或耳旁风上。它没有接受考验。相反，CDC从其网站上删除了任何提及“轶事研究”的内容。锌的哪一部分人们得不到?
科学证据表明，锌是治疗的活性部分，但它需要羟基氯喹(HCQ)进入细胞内杀死病毒。安东尼·卡迪罗医生开的处方是HCQ+锌，他说:“我给每个病人开过这种药，他们的病情都非常非常严重，在8到12小时内，他们基本上没有任何症状。
它是这样工作的。想象一下，你的免疫系统就像马达，HCQ就是燃料泵，锌就是燃料。油泵将加速马达-但只有当油箱里有燃料。
一种快速、安全、可用的治疗方法，只需花费几分钱。它可能拯救10万人的生命和数万亿美元。疾控中心和谁在等什么?
但是我们这里不是在谈论花园品种的锌锭剂。我们说的是200或225毫克硫酸锌，即50毫克元素锌，大约是每日需求量的5倍。然后，通过帮助锌进入细胞，羟氯喹（HCQ）将其乘以5或10倍。因此，您的过量剂量是正常锌每日需求量的25至50倍。拥有所需的所有弹药，您的涡轮增压免疫系统现在可以屠杀 新冠病毒Covid19！ （至少在疾病的早期和中期。在病毒损坏肺部之前，请不要等不及才加油。）
锌是维持健康免疫系统的关键，它可以阻止病原体同时防止炎症。自从1960年代首次报道缺锌症状以来，我们就知道了这一点。[7] 1974年已经描述了锌补充剂的重要性以及像羟氯喹（HCQ）这样的锌转运蛋白在抵御呼吸道病毒中的作用。[8]相信我，HCQ和锌并不是最新的庸俗风尚。锌和对感染的抵抗力之间的联系，正如我们在医学上所知道的一样，是严肃而牢固的。[9]锌本身可能不是灵丹妙药，但锌缺乏会使冠状病毒成为致命的子弹。
锌事实
1.锌在我们的免疫系统中起着至关重要的作用，锌需要适当的锌平衡（稳态）才能杀死细菌和控制炎症。[10]
2.锌可在四个不同的点上阻止病毒复制周期，并特异性地阻断冠状病毒。[11]
3.羟氯喹通过将锌引入需要的细胞中来增加锌的作用。[12]
4.低锌水平与所有这些导致SARS-CoV-2（CoVID-19）死亡的99％以上的慢性疾病有关：—老年，高血压，心脏病，糖尿病，男性，癌症，肥胖，和慢性呼吸道疾病。有关此方面的数据太多，我将其放在附录中。
免疫系统的状态是冠状病毒感染轻症病例和致命性病例背后的动力。这就是为什么Covid-19死亡人数中99％是患有慢性疾病的老年人。他们较弱的免疫系统无法应对新型冠状病毒的挑战，但需要额外的弹药（额外的锌）才能发挥作用。
摘要
我们迫切需要一种新的冠状病毒的治疗方法。自3月中旬以来，几位医生报告称，使用疟疾药物羟氯喹加高剂量的锌可快速治愈高达100％的重症患者。我们需要确认并分享这些结果。因此，根据有关这两种物质的医学文献，我对它们的合理性进行了充分的研究。
自从1960年代以来，锌就一直是我们免疫系统的核心，尽管卫生当局早就忽略了这一点。最近的研究表明，锌在四个不同的点阻止病毒复制，并且锌可对抗冠状病毒。
但是，如果没有转运蛋白或“离子载体”分子使锌进入细胞内部，锌就不容易被生物利用。 2010年，在离子载体的辅助下，锌被证明可阻断细胞中的冠状病毒。它是这样工作的。想象一下，你的免疫系统就像发动机，羟氯喹（HCQ）就是燃料泵，锌就是燃料。油泵将加速马达-但前体是油箱里有燃料。
疟疾药物羟氯喹（HCQ）和氯喹（CQ)在治愈“ Covid-19”方面显示出了希望，大多数情况较轻，但其他研究的结果却不尽相同。由于HCQ也是锌的离子载体，因此许多观察者认为其成功很大程度上是由于它能够动员血液中锌的能力。
冠状病毒死亡中超过99％的死亡发生在与锌缺乏密切相关的慢性病患者中，因此建议补充锌。显然，锌不足会导致疾病的严重性，可以通过足够的生物利用锌来弥补。
因此，我们有一系列事实预测羟氯喹 （HCQ） +锌可以对抗冠状病毒。该疗法根据科学方法验证了该预测。迫切需要立即复制这些结果。
...
澳大利亚研究人员最近证实了锌不仅抑制病毒复制周期的一个阶段，而是四个。体外研究表明，锌可通过多种机制干扰病毒复制周期。其中包括自由病毒灭活（1），抑制病毒脱壳（2），病毒基因组转录（3）以及病毒蛋白翻译和多蛋白加工（4）。” [19]https://medium.com/@leonardjpmail/think-zinc-9c114fde64bf
Add Zinc: From Game-Changer to Game-Winner against Coronavirus
JP Leonard, April 16
Can we Believe Reports of a Sure Cure for SARS-CoV-2?
Here’s the Science behind Hydroxychloroquine plus ZincSee also short subject: How to Stop the Virus And the Quarantines Now and Current project: FieldTrials.net
We are forced to accept terrible damage to our health, economy, and our civil liberties. It’s like “Your Money or Your Life!”
The only happy ending to this nightmare would be a quick cure for the virus. Is a cure being hushed up?
On March 23, talk show host Sean Hannity called up VP Mike Pence on the air about Dr. Vladimir Zelenko’s “miracle drug” cocktail of Hydroxychloroquine, Azithromycin and Zinc. “His results: We have had zero deaths, zero hospitalizations, zero intubations, zero.”
Pence responded, “What we see in some of those anecdotal studies, we’re going to put to the test,” then went on about hydroxychloroquine and vaccines. “Zinc” fell on a blind spot or deaf ear.[2] It was not put to the test. Instead, the CDC stripped any mention of “anecdotal studies” from their website.[3] What part of “Zinc” don’t people get?
Scientific evidence indicates that Zinc is the active part of the treatment, but it needs hydroxychloroquine (HCQ) to get inside cells to kill the virus.[4] Dr. Anthony Cardillo prescribes HCQ+Zinc and says: “Every patient I’ve prescribed it to has been very, very ill and within 8 to 12 hours, they were basically symptom-free.”[5]
Here’s how it works. Imagine your immune system is like the motor, HCQ is the fuel pump, and Zinc is the fuel. The fuel pump will rev up the motor — but only when there’s fuel in the tank.
A quick, safe and available cure, costing pennies to make. It might save 100,000 lives and trillions of dollars. What is the CDC and WHO waiting for?
So much effort is spent on vaccines that won’t be ready until after the pandemic is over, yet no one has time to look at the most promising drug combination we’ve seen? And, compared to HCQ alone, zinc should help those most at risk — 99% of deaths have chronic conditions that are related to zinc deficiency!
What is needed is to quickly and reliably confirm or deny the remarkable claims made for HCQ+Zinc. This ought to be done by a respected institution, but until then, individual doctors can do more. Ask your doctors to try HCQ+zinc on their Coronavirus patients. Send them the link to this article, post it on social media. We need to put pressure on them to give this treatment a try. We have been locked down long enough. We can’t live on air, going deeper in debt by printing more trillions each month. It’s not about partisan politics. We’re all in the same boat.
To be fair, Trump probably saved thousands of lives by “touting the off-label drug HCQ,” making it the most popular treatment among doctors around the world.[6] And in his April 8th press conference, he did say “You should add zinc.” But the prevailing attitude in the medical field is very skeptical. HCQ is not highly regarded, and zinc is just a nutritional supplement, so how could these two do anything? This is a hasty assumption, not a science-based conclusion. That’s why I did this research, to document the established scientific basis for zinc therapy, and try to get people to at least be open to trying it.
Another ingrained habit is dismissing key evidence as “anecdotal.” By anecdote do they mean it’s funny? Doctors and patients are not joking with stories like this. A patient getting seriously sicker and sicker for 15 days. On the 16th day they get the new treatment, and suddenly they get better. What are the odds? A lot less than one in 16. In fact, this is considered solid proof when it happens in a clinical trial. But for now, let’s give the coincidence theory 50% odds it was just chance. So then you have 10 patients in a row that recover with the same treatment. The odds of that happening by chance are 1 in 2¹⁰. One in a thousand. Go back and take the one in 16 chance 10 times over, the odds are one in a trillion.
You just don’t need trials of thousands of cases to see what’s self-evident. Each patient is important. This anecdotal rejection fallacy is a form of denial, a way of denying common sense and telling us that we are just imagining things. It’s not really thinking, it’s just a habit of thinking in a box. But to prove the point, we need to document results better.
Open your mind and “Think Zinc” for a little while. So happens, there’s a lot of this humble gray mineral right in our gray matter! :-) Yet it isn’t the kind of sexy, fascinating product to fire imaginations, galvanize a task force into action, or hype your stock for the next new vaccine IPO. Big Pharma doesn’t run TV ads enticing you to plant healthy garden vegetables, either.
But we’re not talking here about garden variety zinc lozenges. We’re talking about a dose of 200 or 225 mg of zinc sulfate, that’s 50 mg of elemental zinc, about 5 times the daily requirement. Then, by helping zinc enter your cells, HCQ multiplies that by 5 or 10 x. So you’re getting a superdose of 25 to 50 times the normal daily requirement of zinc. Armed with all the ammo it needs, your turbocharged immune system is now ready to slaughter Covid19! (At least in the early and middle stages of the disease. Do not wait to tank up until the virus has damaged the lungs.)
Zinc is the key to a healthy immune system, blocking pathogens while preventing inflammation. We’ve known this since zinc deficiency symptoms were first reported in the 1960's.[7] The importance of zinc supplements and the role of zinc transporters like HCQ in fending off respiratory viruses was described already in 1974.[8] Trust me, HCQ and zinc are not the latest quack fad. The link between zinc and resistance to infection, is as serious and solid as anything we know in medicine.[9] Zinc on its own may not be a silver bullet — but zinc deficiency can make coronavirus into a fatal bullet.
Zinc Facts
1. Zinc plays a central, crucial role in our immune system, which needs the right balance of zinc (homeostasis) both to kill germs and to control inflammation.[10]
2. Zinc blocks the virus replication cycle at four different points, and to specifically blocks coronaviruses.[11]
3. Hydroxychloroquine multiplies the effect of zinc by bringing it into cells where it’s needed.[12]
4. Low zinc levels are linked to all these chronic conditions that account for over 99% of deaths from SARS-CoV-2 (CoVID-19): — old age, hypertension, heart disease, diabetes, male gender, cancer, obesity, and chronic respiratory disease. There’s so much data on this I put it in the Appendix.
The immune system is what makes all the difference between a mild case of coronavirus and a fatal one. It’s why 99% of Covid-19 fatalities deaths are older people with chronic conditions. Their weaker immune system is not up to the challenge of the novel coronavirus, but with extra ammunition — extra zinc — it should do the job.
Summary Abstract
We are in urgent need of a cure for the novel coronavirus. Since mid-March, several physicians report curing up to 100% of seriously ill patients quickly with the malaria drug hydroxychloroquine plus high doses of zinc. We need to confirm and share these results. Accordingly, I have thoroughly researched their plausibility in line with the medical literature on the two substances.
We’ve known Zinc is central to our immune system since the 1960’s, although health authorities have long ignored this. Recent research shows that zinc blocks virus replication at four different points, and that zinc works against coronaviruses.
However, zinc is not readily bio-available without a transporter or “ionophore” molecule to get it inside the cells. In 2010, zinc was shown to block coronaviruses in cells when assisted by an ionophore.
The malaria drug Hydroxychloroquine (HCQ) has shown some promise in curing “Covid-19”, mostly with milder cases, but with mixed outcomes in other studies. Since HCQ is also an ionophore of zinc, many observers hypothesize that its success is largely due to its ability to mobilize what zinc is present in the bloodstream.
Over 99% of deaths from coronavirus occur in patients with chronic conditions which are strongly linked to zinc deficiency, and for which zinc supplementation is recommended. The implication is clear that insufficient zinc contributes to severity of the illness, which might be remedied with sufficient bio-available zinc.
Thus we have an array of facts predicting that HCQ + Zinc could work against the coronavirus. The therapy validates the prediction, in line with scientific method. It is urgent to replicate these results without further delay.
...
Australian researchers recently established not only one but four “diverse stages of viral replication cycles that are inhibited by zinc. In vitro studies have demonstrated a number of mechanisms by which zinc interferes with the viral replication cycle. These include free virus inactivation (1), inhibition of viral uncoating (2), viral genome transcription (3), and viral protein translation and polyprotein processing (4).”[19]
https://medium.com/@leonardjpmail/think-zinc-9c114fde64bf
Chronic Respiratory Disease
Deficient Zinc Transport in Lungs Linked to COPD, Cystic Fibrosis, Study Finds
https://copdnewstoday.com/2018/01/11/deficient-zinc-transport-in-lungs-linked-to-copd-cystic-fibrosis/
“Zinc deficiency in the lung causes overproduction of mucus and is associated with respiratory diseases such as chronic obstructive pulmonary disease (COPD)”
Zinc deficiency has been known of for 40 years but ignored by global health organisations, by Ananda S. Prasad, 2003 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1125304/ See also: Discovery of Human Zinc Deficiency: Its Impact on Human Health and Disease https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3649098/ “The essentiality of zinc in humans was established in 1963… The major factor contributing to zinc deficiency is high phytate-containing cereal protein intake,” This could be one reason that carbohydrates are linked to shorter life span.
[5] LA doctor seeing success with hydroxychloroquine to treat COVID-19
https://abc7news.com/coronavirus-drug-covid-19-malaria-hydroxychloroquine/6079864/
[9] Zinc as a Gatekeeper of Immune Function,
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5748737/
“After the discovery of zinc deficiency in the 1960s, it soon became clear that zinc is essential for the function of the immune system. Zinc ions are involved in regulating intracellular signaling pathways in innate and adaptive immune cells. Zinc homeostasis is largely controlled via the expression and action of zinc “importers” (ZIP 1–14) … Here, we report molecular mechanisms underlying the development of a pro-inflammatory phenotype during zinc deficiency. Furthermore, we describe links between altered zinc homeostasis and disease development. Consequently, the benefits of zinc supplementation for a malfunctioning immune system become clear.”
It is true that viruses can sometimes exploit excess zinc to replicate their own proteins, but this is the exception to the rule, as the level of free zinc in cells is very tightly controlled; too much of it becomes toxic.See: Role of Zn2+ Ions in Host-Virus Interactions https://jvi.asm.org/content/82/23/11486
[10] The Role of Zinc in Antiviral Immunity https://academic.oup.com/advances/article/10/4/696/5476413
“Zinc status is a critical factor that can influence antiviral immunity, particularly as zinc-deficient populations are often most at risk of acquiring viral infections”
[11] Effect of Zinc Salts on Respiratory Syncytial Virus Replication https://www.ncbi.nlm.nih.gov/pmc/articles/PMC353050/
“Zinc supplementation decreases the morbidity of lower respiratory tract infection “
[12] Zn(2+) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture. (Dutch study) https://www.ncbi.nlm.nih.gov/pubmed/21079686 “Increasing the intracellular Zn(2+) concentration with zinc-ionophores like pyrithione (PT) can efficiently impair the replication of a variety of RNA viruses.”
[13] Why is the coronavirus so much more deadly for men than for women? https://www.latimes.com/science/story/2020-03-21/why-is-the-coronavirus-more-deadly-for-men-than-for-women “Italian health authorities last week reported that among 13,882 cases of COVID-19 and 803 deaths between Feb. 21 and Mar. 12, men accounted for 58% of all cases and 72% of deaths.”
[19] The Role of Zinc in Antiviral Immunity (April 2019, Australian paper)
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6628855/ caption to Figure 1. With thanks to Dr. Eric Beeth for this important source
[20] Ibid. Zinc as a Gatekeeper of Immune Function, https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5748737/
[22] Ibid. Zn(2+) inhibits coronavirus and arterivirus RNA polymerase activity in vitro and zinc ionophores block the replication of these viruses in cell culture. (Dutch study) https://www.ncbi.nlm.nih.gov/pubmed/21079686
[23] COVID-19 Update 8: Zinc and chloroquine for the treatment of COVID-19? (WebCram) https://www.youtube.com/watch?v=BIymfznD7YA I have transcribed key portions of the narrative here https://blogs.sciencemag.org/pipeline/archives/2020/04/06/hydroxychloroquine-update-for-april-6
[25] Nevada MD Armen Nikogosian explains why zinc ionophore therapy works
https://www.theepochtimes.com/old-drug-may-provide-promising-new-treatment-for-covid-19_3277523.html
[42] Quercetin as an Antiviral Agent Inhibits Influenza A Virus (IAV) Entry
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4728566/
Zinc ionophore activity of quercetin and epigallocatechin-gallate: from Hepa 1–6 cells to a liposome model.
https://www.ncbi.nlm.nih.gov/pubmed/25050823
“quercetin may serve as an effective oral immunomodulator for improving cell-mediated immune defense”
https://www.ncbi.nlm.nih.gov/pubmed/32184034
[43] https://nutritionalpharmacology.wordpress.com/2020/03/21/combating-covid-19-with-zinc-and-quercetin/
[53] http://www.progressivepress.com/news/common-sense-vs-coronavirus
April 17 My friend Kevin Barrett interviewed me about this story on his Noliesradio.org talk show today. We had a great time.
I see where the government has discovered that sunlight kills the coronavirus quickly. Yes people knew that from the 1918 Spanish flu, if not millenia earlier. So is that why we’re supposed to stay indoors.Just came across an article by Bill Sardi, longtime expert on nutritional supplements. He notes that Trump recommended adding zinc therapy in an April 8 press conference https://www.lewrockwell.com/2020/04/bill-sardi/modern-medicine-ridicules-presidents-coronavirus-drug-plus-zinc-saying-there-is-no-evidence-when-decade-old-study-goes-ignored/
Sardi: “An online search (April 12) at the National Library of Medicine reveals 62 published reports dating back to 1987 involving chloroquine and coronaviruses, but inexplicably none mention zinc. Nor do product inserts list chloroquine as a zinc ionophore. This is a giant scientific oversight.” Behold the Great Zinc Blind Spot. “An emergency room physician’s list of signs and symptoms caused by COVID-19 coronavirus mirror all the signs of zinc deficiency.”
Zinc Deficiency During Pregnancy Leads to Altered Microbiome and Elevated Inflammatory Markers in Mice
Ulm University, Ulm, Germany.
Zinc is an essential trace metal for bacteria of the intestinal flora. Approximately 20% of dietary zinc - intake is used by intestinal bacteria. The microbiome has recently been described as an important factor for healthy brain function via so-called gut-brain interactions. Similarly, zinc deficiency has been associated with neurological problems such as depression, mental lethargy and cognitive impairments in humans and animal models. However, the underlying pathomechanisms are currently not well understood and a link between zinc deficiency and altered microbiota composition has not been studied. Especially during pregnancy, women may be prone to low zinc status. Thus, here, we investigate whether zinc deficiency alters gut-brain interaction in pregnant mice by triggering changes in the microbiome. To that end, pregnant mice were fed different diets being zinc-adequate, deficient in zinc, or adequate in zinc but high in zinc uptake antagonists for 8 weeks. Our results show that acute zinc-deficient pregnant mice and pregnant mice on a diet high in zinc uptake antagonists have an altered composition of gastro-intestinal (GI) microbiota. These changes were accompanied by alterations in markers for GI permeability. Within the brain, we found signs of neuroinflammation. Interestingly, microbiota composition, gut pathology, and inflammatory cytokine levels were partially rescued upon supplementation of mice with zinc amino-acid conjugates (ZnAA). We conclude that zinc deficiency may contribute to abnormal gut-brain signaling by altering gut physiology, microbiota composition and triggering an increase of inflammatory markers.妊娠期缺锌导致小鼠微生物群改变和炎症标志物升高
锌是肠道菌群必需的微量金属。膳食中大约20%的锌被肠道细菌吸收。最近，通过所谓的肠道-大脑相互作用，微生物组被认为是健康大脑功能的重要因素。同样，在人类和动物模型中，缺锌也与神经系统问题有关，如抑郁、精神萎靡和认知障碍。然而，潜在的发病机制目前还不清楚，缺锌和改变的微生物群组成之间的联系也没有研究。特别是在怀孕期间，妇女可能容易出现低锌状态。因此，在这里，我们研究锌缺乏是否通过触发微生物组的变化来改变怀孕小鼠的肠道-大脑相互作用。为此，怀孕小鼠被喂食足锌、缺锌或足锌但高锌拮抗剂摄取量的不同饮食8周。我们的研究结果表明，急性锌缺乏的怀孕小鼠和高锌吸收拮抗剂饮食的怀孕小鼠的胃肠道(GI)菌群组成改变。这些变化伴随着胃肠道通透性标志物的改变。在大脑内部，我们发现了神经炎症的迹象。有趣的是，给小鼠补充氨基酸结合物锌(ZnAA)后，微生物群组成、肠道病理和炎症细胞因子水平得到了部分恢复。我们的结论是，缺锌可能通过改变肠道生理、微生物群组成和触发炎症标志物的增加而导致肠道-大脑信号异常。Zinc Deficiency During Pregnancy Leads to Altered Microbiome and Elevated Inflammatory Markers in Mice - PubMed
https://pubmed.ncbi.nlm.nih.gov/31849598/
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https://www.microbiologyresearch.org/content/journal/jgv/10.1099/jgv.0.000982Enterovirus A71 (EV-A71) is a positive-strand RNA virus that causes hand-foot-mouth disease and neurological complications in children and infants. Although the underlying mechanisms remain to be further defined, impaired immunity is thought to play an important role. The host zinc-finger antiviral protein (ZAP), an IFN-stimulated gene product, has been reported to specifically inhibit the ...
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Jan 03, 2018 · AsianScientist (Jan. 3, 2018) – A team of scientists in Japan has discovered that the genes involved in zinc transport play a role in respiratory diseases such as chronic obstructive pulmonary disease (COPD) and cystic fibrosis (CF). They published their findings in …
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Oct 16, 2013 · One critical micronutrient needed by preterm infants is zinc. Zinc has an important and well-established role in immune function and growth ( 2 ). Evidence suggests that the amount of zinc in human milk, like that of other minerals such as calcium and phosphorus, may not be optimal for very preterm infants and that human-milk feedings should be fortified with additional zinc for this …
Zinc in Early Life: A Key Element in the Fetus and Preterm ...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4690094Dec 11, 2015 · Zinc requirements for term infants are estimated to be 0.8 mg/day, whereas preterm neonates may require up to 3 mg/kg per day to achieve adequate zinc retention . Less variability regarding intravenous supplementation may be found in the recommendations of different scientific societies and committees.
Zinc concentration in preterm newborns at term age, a ...
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6782045Sep 13, 2019 · Zinc is essential for enzyme function in individuals of all ages, including preterm infants. The typical symptoms of zinc deficiency usually develop after three continuous months of low serum zinc concentration (SZC) and include failure to thrive, poor weight gain, periorificial dermatitis, glossitis and increased susceptibility to infections. 1 Regardless of the clinical severity of this deficiency, the role played by zinc in the growth of preterm newborns …
