View Affiliations Affiliations: I. This is an open access article distributed under the terms of Creative Commons Attribution License. Zinc is known to modulate antiviral and antibacterial immunity and regulate inflammatory response. This effect may underlie therapeutic efficiency of chloroquine known to act as zinc ionophore.
However, further clinical and experimental studies are required. Introduction Zinc is an essential metal being involved in a variety of biological processes due to its function as a cofactor, signaling molecule, and structural element.
It is involved in the regulation of carbohydrate and lipid metabolism, as well as the functioning of the reproductive, cardiovascular, and nervous system 1. At the same time, the most critical role of zinc is demonstrated for the immune system.
Briefly, zinc regulates proliferation, differentiation, maturation, and functioning of leukocytes and lymphocytes 2.
Zinc plays a signaling role involved in the modulation of inflammatory responses 3. It is also a component of nutritional immunity 4. Correspondingly, alteration of zinc status significantly affects immune response resulting in increased susceptibility to inflammatory and infectious diseases including acquired immune deficiency syndrome, measles, malaria, tuberculosis, and pneumonia 5.
Earlier data demonstrate that populational Zn status is associated with the prevalence of respiratory tract infections in children and adults 67. Moreover, certain groups of people, including infants, especially preterm ones, and elderly, are considered to be at high risk of zinc deficiency and its adverse effects 9.
Under zinc deficiency condition, organisms are more susceptible to toxin-producing bacteria or enteroviral pathogens that activate guanylate and adenylate cyclases, stimulating chloride secretion, causing diarrhea and diminishing absorption of nutrients, thus exacerbating an already compromised mineral status. In addition, zinc deficiency may impair the absorption of water and electrolytes, delaying the termination of normally self-limiting gastrointestinal disease episodes During chronic deficiency, the production of pro-inflammatory cytokines increases, influencing the outcome of a large number of inflammatory, metabolic, neurodegenerative and immune diseases Diseases such as rheumatoid arthritis, diabetes 12atherosclerosis and obesity 13impaired cognitive function 14as well as age-related macular degeneration AMD may be due to zinc deficiency, worsening chronic inflammation and triggering oxidative stress.
The viruses from the Coronaviridae family are zoonotic viruses that can be transmitted from animals to humans. The bat is considered the reservoir for these viruses, but other intermediate animals can also transmit the virus to humans Currently, the prevalence of COVID exceeds 1, cases resulting in 92, deaths worldwide COVID predominantly affects the respiratory system resulting in pneumonia and acute respiratory distress syndrome 24leading to the requirement of mechanical ventilation The risk is also increased by modern life in which individuals are exposed to a multitude of chemicals, even in low doses that in the long-term predispose to chronic diseases and metabolic disturbances 27 - Preexisting chronic metabolic diseases including diabetes, cardiovascular diseases 32and obesity 33 are considered as risk factors for increased COVID susceptibility and mortality.
Due to the clearly demonstrated role of zinc in immunity 2and impaired zinc status in ageing 35metabolic diseases including diabetes, obesity, and cardiovascular diseases 13it is speculated that zinc compounds may be used as an adjunct therapy in COVID treatment 36 for increasing antiviral resistance Of note, zinc was earlier suggested as the potential agent for immune support and prevention of H1N1 influenza 'swine flu' Zinc is considered as the potential supportive treatment in therapy of COVID infection due to its immune modulatory effect, as well as direct antiviral effect However, the existing data will be only mechanistically discussed in this review, as direct data on anti-COVID effects of zinc are absent to date.
Of note, recent trials have indicated efficiency of chloroquine antiviral activity as a treatment of COVID 40although the intimate mechanisms of its antiviral activity require further investigation Moreover, the authors also propose that chloroquine-mediate zinc influx may underlie anticancer activity of the compound In this view zinc supplementation without chloroquine might have similar positive effects diabetes metabolism and obesity journal adverse side-effects of chloroquine treatment Hypothetically, such an effect may be also observed using other zinc ionophores like quercetin and epigallocatechin-gallate 44 with substantially lower toxicity, although clinical trials supported by experimental in vitro studies are required to support this hypothesis.
In view of the presence of similar critical Zn-containing sites, Zn-ejector drugs e.
Elevated Serum IP-10 Levels Observed in Type 1 Diabetes
Speth et al 50 demonstrated that zinc exposure µM was shown to reduce recombinant human ACE-2 activity in rat lungs. Although this concentration is close to physiological values of total zinc, the modulating effect of zinc on SARS-CoVACE2 interaction seem to be only hypothetical The latter may not only alter viral particle removal, but also predispose to bacterial co-infection as observed for influenza virus In turn, Zn supplementation was shown to improve ciliary length in bronchial epithelium of Csehország resort cukorbetegség rats 55as well as increase ciliary beat frequency in vitro Therefore, zinc may hypothetically ameliorate nCoVinduced dysfunction of mucociliary clearance.
Generally, zinc was shown to be essential for respiratory epithelium due to antioxidant and anti-inflammatory activity 57as well as regulation of tight junction diabetes metabolism and obesity journal ZO-1 and Claudin-1 58thus increasing its barrier functions. In turn, downregulation of tight junction protein complexes e. In addition, loss of TJ perm selectivity in the airways results in an un-controlled leakage of high molecular weight proteins and water into the airways, which results in the formation of alveolar edema cukor intolerancia ARDS Zinc was shown to have a significant impact on viral infections through modulation of viral particle entry, fusion, replication, viral protein translation and further release for a number of viruses including those involved in respiratory system pathology 37 Specifically, increasing intracellular Zn levels through application of Zn ionophores such as pyrithione and hinokitiol significantly alters replication of picornavirus, the leading cause of common cold