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1.
J Inorg Biochem ; 231: 111777, 2022 06.
Article in English | MEDLINE | ID: covidwho-1873158

ABSTRACT

The Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) pandemic is currently the major challenge to global public health. Two proteases, papain-like protease (PLpro) and the 3-chymotrypsin-like protease (3CLpro or Mpro), are indispensable for SARS-CoV-2 replication, making them attractive targets for antiviral therapy development. Here we screened a panel of essential metal ions using a proteolytic assay and identified that zinc gluconate, a widely-used zinc supplement, strongly inhibited the proteolytic activities of the two proteases in vitro. Biochemical and crystallographic data reveal that zinc gluconate exhibited the inhibitory function via binding to the protease catalytic site residues. We further show that treatment of zinc gluconate in combination with a small molecule ionophore hinokitiol, could lead to elevated intracellular Zn2+ level and thereby significantly impaired the two protease activities in cellulo. Particularly, this approach could also be applied to rescue SARS-CoV-2 infected mammalian cells, indicative of potential application to combat coronavirus infections. Our studies provide the direct experimental evidence that elevated intracellular zinc concentration directly inhibits SARS-CoV-2 replication and suggest the potential benefits to use the zinc supplements for coronavirus disease 2019 (COVID-19) treatment.


Subject(s)
COVID-19 , SARS-CoV-2 , Animals , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , COVID-19/drug therapy , Gluconates , Mammals/metabolism , Monoterpenes , Peptide Hydrolases/metabolism , Tropolone/analogs & derivatives , Zinc/pharmacology
2.
Int J Mol Sci ; 23(6)2022 Mar 10.
Article in English | MEDLINE | ID: covidwho-1742487

ABSTRACT

The published literature makes a very strong case that a wide range of disease morbidity associates with and may in part be due to epithelial barrier leak. An equally large body of published literature substantiates that a diverse group of micronutrients can reduce barrier leak across a wide array of epithelial tissue types, stemming from both cell culture as well as animal and human tissue models. Conversely, micronutrient deficiencies can exacerbate both barrier leak and morbidity. Focusing on zinc, Vitamin A and Vitamin D, this review shows that at concentrations above RDA levels but well below toxicity limits, these micronutrients can induce cell- and tissue-specific molecular-level changes in tight junctional complexes (and by other mechanisms) that reduce barrier leak. An opportunity now exists in critical care-but also medical prophylactic and therapeutic care in general-to consider implementation of select micronutrients at elevated dosages as adjuvant therapeutics in a variety of disease management. This consideration is particularly pointed amidst the COVID-19 pandemic.


Subject(s)
Inflammatory Bowel Diseases/metabolism , Intestinal Mucosa/metabolism , Micronutrients/metabolism , Vitamin A/metabolism , Vitamin D/metabolism , Zinc/metabolism , Animals , COVID-19/epidemiology , COVID-19/metabolism , COVID-19/virology , Humans , Micronutrients/pharmacology , Pandemics/prevention & control , SARS-CoV-2/physiology , Tight Junctions/drug effects , Tight Junctions/metabolism , Vitamin A/pharmacology , Vitamin D/pharmacology , Vitamins/metabolism , Vitamins/pharmacology , Zinc/pharmacology
3.
J Inorg Biochem ; 228: 111691, 2022 03.
Article in English | MEDLINE | ID: covidwho-1558451

ABSTRACT

Zinc can play a pathophysiological role in several diseases and can interfere in key processes of microbial growth. This evidence justifies the efforts in applying Zinc ionophores to restore Zinc homeostasis and treat bacterial/viral infections such as coronavirus diseases. Zinc ionophores increase the intracellular concentration of Zinc ions causing significant biological effects. This review provides, for the first time, an overview of the applications of the main Zinc ionophores in Zinc deficiency, infectious diseases, and in cancer, discussing the pharmacological and coordination properties of the Zinc ionophores.


Subject(s)
Communicable Diseases/drug therapy , Ionophores/chemistry , Neoplasms/drug therapy , Zinc/chemistry , Zinc/pharmacology , Acrodermatitis/drug therapy , Anti-Bacterial Agents/pharmacology , Antineoplastic Agents/pharmacology , Antiviral Agents/pharmacology , COVID-19/drug therapy , Homeostasis/drug effects , Humans , Ionophores/pharmacology , Zinc/deficiency
4.
Molecules ; 26(21)2021 Oct 31.
Article in English | MEDLINE | ID: covidwho-1488679

ABSTRACT

Zinc is the second most abundant trace element in the human body, and it plays a fundamental role in human physiology, being an integral component of hundreds of enzymes and transcription factors. The discovery that zinc atoms may compete with copper for their absorption in the gastrointestinal tract let to introduce zinc in the therapy of Wilson's disease, a congenital disorder of copper metabolism characterized by a systemic copper storage. Nowadays, zinc salts are considered one of the best therapeutic approach in patients affected by Wilson's disease. On the basis of the similarities, at histological level, between Wilson's disease and non-alcoholic liver disease, zinc has been successfully introduced in the therapy of non-alcoholic liver disease, with positive effects both on insulin resistance and oxidative stress. Recently, zinc deficiency has been indicated as a possible factor responsible for the susceptibility of elderly patients to undergo infection by SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic. Here, we present the data correlating zinc deficiency with the insurgence and progression of Covid-19 with low zinc levels associated with severe disease states. Finally, the relevance of zinc supplementation in aged people at risk for SARS-CoV-2 is underlined, with the aim that the zinc-based drug, classically used in the treatment of copper overload, might be recorded as one of the tools reducing the mortality of COVID-19, particularly in elderly people.


Subject(s)
Liver/drug effects , Liver/injuries , Zinc/pharmacology , COVID-19/complications , COVID-19/drug therapy , Chelating Agents/metabolism , Copper/metabolism , Hepatolenticular Degeneration/complications , Hepatolenticular Degeneration/drug therapy , Hepatolenticular Degeneration/metabolism , Humans , Liver/metabolism , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , SARS-CoV-2/pathogenicity , Zinc/deficiency , Zinc/metabolism
5.
ScientificWorldJournal ; 2021: 9632034, 2021.
Article in English | MEDLINE | ID: covidwho-1438139

ABSTRACT

The world is currently grappling with the coronavirus disease (COVID-19) pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). The infection can cause fever, a dry cough, fatigue, severe pneumonia, respiratory distress syndrome, and in some cases death. There is currently no effective antiviral SARS-CoV-2 drug. To reduce the number of infections and deaths, it is critical to focus on strengthening immunity. This review aims to conduct a comprehensive search on the previous studies using Google Scholar, ScienceDirect, Medline, PubMed, and Scopus for the collection of research papers based on the role of zinc in the immune system, the antiviral activity of zinc, the effect of zinc supplementation in respiratory infections, the therapeutic approaches against viral infections based on medicinal plants, and the role of plants' bioactive molecules in fighting viral infections. In conclusion, we highlighted the pivotal role of zinc in antiviral immunity and we suggested the bioactive molecules derived from medicinal plants as a search matrix for the development of anti-SARS-CoV-2 drugs.


Subject(s)
COVID-19/drug therapy , Plant Extracts/pharmacology , Plants, Medicinal/chemistry , SARS-CoV-2/drug effects , Zinc/pharmacology , COVID-19/epidemiology , COVID-19/virology , Humans , Immune System/drug effects
6.
J Gen Virol ; 102(4)2021 04.
Article in English | MEDLINE | ID: covidwho-1393559

ABSTRACT

Reactive oxygen species (ROS) are chemically active species which are involved in maintaining cellular and signalling processes at physiological concentrations. Therefore, cellular components that regulate redox balance are likely to play a crucial role in viral life-cycle either as promoters of viral replication or with antiviral functions. Zinc is an essential micronutrient associated with anti-oxidative systems and helps in maintaining a balanced cellular redox state. Here, we show that zinc chelation leads to induction of reactive oxygen species (ROS) in epithelial cells and addition of zinc restores ROS levels to basal state. Addition of ROS (H2O2) inhibited dengue virus (DENV) infection in a dose-dependent manner indicating that oxidative stress has adverse effects on DENV infection. ROS affects early stages of DENV replication as observed by quantitation of positive and negative strand viral RNA. We observed that addition of ROS specifically affected viral titres of positive strand RNA viruses. We further demonstrate that ROS specifically altered SEC31A expression at the ER suggesting a role for SEC31A-mediated pathways in the life-cycle of positive strand RNA viruses and provides an opportunity to identify drug targets regulating oxidative stress responses for antiviral development.


Subject(s)
Dengue Virus/drug effects , Hydrogen Peroxide/pharmacology , Reactive Oxygen Species/pharmacology , Virus Replication , Zinc/pharmacology , Adolescent , Aedes , Animals , Caco-2 Cells , Child , Child, Preschool , Chlorocebus aethiops , Cricetinae , Dengue/virology , Dengue Virus/physiology , Humans , Oxidative Stress , RNA, Viral
7.
ACS Appl Mater Interfaces ; 13(26): 30317-30325, 2021 Jul 07.
Article in English | MEDLINE | ID: covidwho-1387130

ABSTRACT

Influenza A viruses (IAV) and SARS-CoV-2 can spread via liquid droplets and aerosols. Face masks and other personal protective equipment (PPE) can act as barriers that prevent the spread of these viruses. However, IAV and SARS-CoV-2 are stable for hours on various materials, which makes frequent and correct disposal of these PPE important. Metal ions embedded into PPE may inactivate respiratory viruses, but confounding factors such as adsorption of viruses make measuring and optimizing the inactivation characteristics difficult. Here, we used polyamide 6.6 (PA66) fibers containing embedded zinc ions and systematically investigated if these fibers can adsorb and inactivate SARS-CoV-2 and IAV H1N1 when woven into a fabric. We found that our PA66-based fabric decreased the IAV H1N1 and SARS-CoV-2 titer by approximately 100-fold. Moreover, we found that the zinc content and the virus inactivating property of the fabric remained stable over 50 standardized washes. Overall, these results provide insights into the development of reusable PPE that offer protection against RNA virus spread.


Subject(s)
Influenza A virus/physiology , Nylons/pharmacology , SARS-CoV-2/physiology , Textiles , Virus Inactivation/drug effects , Zinc/pharmacology , Adsorption , Animals , Chlorocebus aethiops , Cotton Fiber , Dogs , HEK293 Cells , Humans , Influenza A virus/drug effects , Ions , Madin Darby Canine Kidney Cells , Polypropylenes/pharmacology , SARS-CoV-2/drug effects , Vero Cells , Viral Load , Zinc Oxide/pharmacology
9.
Dalton Trans ; 50(35): 12226-12233, 2021 Sep 14.
Article in English | MEDLINE | ID: covidwho-1358359

ABSTRACT

Numerous organic molecules are known to inhibit the main protease of SARS-CoV-2, (SC2Mpro), a key component in viral replication of the 2019 novel coronavirus. We explore the hypothesis that zinc ions, long used as a medicinal supplement and known to support immune function, bind to the SC2Mpro enzyme in combination with lipophilic tropolone and thiotropolone ligands, L, block substrate docking, and inhibit function. This study combines synthetic inorganic chemistry, in vitro protease activity assays, and computational modeling. While the ligands themselves have half maximal inhibition concentrations, IC50, for SC2Mpro in the 8-34 µM range, the IC50 values are ca. 100 nM for Zn(NO3)2 which are further enhanced in Zn-L combinations (59-97 nM). Isolation of the Zn(L)2 binary complexes and characterization of their ability to undergo ligand displacement is the basis for computational modeling of the chemical features of the enzyme inhibition. Blind docking onto the SC2Mpro enzyme surface using a modified Autodock4 protocol found preferential binding into the active site pocket. Such Zn-L combinations orient so as to permit dative bonding of Zn(L)+ to basic active site residues.


Subject(s)
COVID-19/drug therapy , Coronavirus 3C Proteases/antagonists & inhibitors , Protease Inhibitors/pharmacology , SARS-CoV-2/drug effects , Tropolone/pharmacology , Zinc/pharmacology , Antiviral Agents/chemistry , Antiviral Agents/pharmacology , COVID-19/virology , Catalytic Domain/drug effects , Coronavirus 3C Proteases/chemistry , Coronavirus 3C Proteases/metabolism , Humans , Ligands , Models, Molecular , Molecular Docking Simulation , Protease Inhibitors/chemistry , SARS-CoV-2/enzymology , Tropolone/analogs & derivatives , Zinc/chemistry
10.
Biomed Pharmacother ; 142: 111956, 2021 Oct.
Article in English | MEDLINE | ID: covidwho-1330661

ABSTRACT

Novel coronavirus 2019 (COVID-19) is a zoonosis that revised the global economic and societal progress since early 2020. The SARS-CoV-2 has been recognized as the responsible pathogen for COVID-19 with high infection and mortality rate potential. It has spread in 192 countries and infected about 1.5% of the world population, and still, a proper therapeutic approach is not unveiled. COVID-19 indication starts with fever to shortness of breathing, leading to ICU admission with the ventilation support in severe conditions. Besides the symptomatic mainstay clinical therapeutic approach, only Remdesivir has been approved by the FDA. Several pharmaceutical companies claimed different vaccines with exceptionally high efficacy (90-95%) against COVID-19; how long these vaccines can protect and long-term safety with the new variants are unpredictable. After the worldwide spread of the COVID-19 pandemic, numerous clinical trials with different phases are being performed to find the most appropriate solution to this condition. Some of these trials with old FDA-approved drugs showed promising results. In this review, we have precisely compiled the efforts to curb the disease and discussed the clinical findings of Ivermectin, Doxycycline, Vitamin-D, Vitamin-C, Zinc, and cannabidiol and their combinations. Additionally, the correlation of these molecules on the prophylactic and diseased ministration against COVID-19 has been explored.


Subject(s)
COVID-19/drug therapy , Cannabidiol/pharmacology , SARS-CoV-2 , Antiviral Agents/pharmacology , Ascorbic Acid/pharmacology , COVID-19/epidemiology , COVID-19/prevention & control , Dietary Supplements , Doxycycline/pharmacology , Drug Repositioning/methods , Drug Therapy, Combination/methods , Humans , Ivermectin , SARS-CoV-2/drug effects , SARS-CoV-2/isolation & purification , Treatment Outcome , Vitamin D/pharmacology , Zinc/pharmacology
11.
ACS Appl Mater Interfaces ; 13(26): 30317-30325, 2021 Jul 07.
Article in English | MEDLINE | ID: covidwho-1284676

ABSTRACT

Influenza A viruses (IAV) and SARS-CoV-2 can spread via liquid droplets and aerosols. Face masks and other personal protective equipment (PPE) can act as barriers that prevent the spread of these viruses. However, IAV and SARS-CoV-2 are stable for hours on various materials, which makes frequent and correct disposal of these PPE important. Metal ions embedded into PPE may inactivate respiratory viruses, but confounding factors such as adsorption of viruses make measuring and optimizing the inactivation characteristics difficult. Here, we used polyamide 6.6 (PA66) fibers containing embedded zinc ions and systematically investigated if these fibers can adsorb and inactivate SARS-CoV-2 and IAV H1N1 when woven into a fabric. We found that our PA66-based fabric decreased the IAV H1N1 and SARS-CoV-2 titer by approximately 100-fold. Moreover, we found that the zinc content and the virus inactivating property of the fabric remained stable over 50 standardized washes. Overall, these results provide insights into the development of reusable PPE that offer protection against RNA virus spread.


Subject(s)
Influenza A virus/physiology , Nylons/pharmacology , SARS-CoV-2/physiology , Textiles , Virus Inactivation/drug effects , Zinc/pharmacology , Adsorption , Animals , Chlorocebus aethiops , Cotton Fiber , Dogs , HEK293 Cells , Humans , Influenza A virus/drug effects , Ions , Madin Darby Canine Kidney Cells , Polypropylenes/pharmacology , SARS-CoV-2/drug effects , Vero Cells , Viral Load , Zinc Oxide/pharmacology
12.
Life Sci ; 280: 119752, 2021 Sep 01.
Article in English | MEDLINE | ID: covidwho-1281493

ABSTRACT

AIMS: Angiotensin-converting enzyme 2 (ACE2) is a key negative regulator of the renin-angiotensin system and also a major receptor for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Here, we reveal a role for NF-κB in human lung cell expression of ACE2, and we further explore the potential utility of repurposing NF-κB inhibitors to downregulate ACE2. MAIN METHODS: Expression of ACE2 was assessed by Western blotting and RT-qPCR in multiple human lung cell lines with or without NF-κB inhibitor treatment. Surface ACE2 expression and intracellular reactive oxygen species (ROS) levels were measured with flow cytometry. p50 was knocked down with siRNA. Cytotoxicity was monitored by PARP cleavage and MTS assay. KEY FINDINGS: Pyrrolidine dithiocarbamate (PDTC), an NF-κB inhibitor, suppressed endogenous ACE2 mRNA and protein expression in H322M and Calu-3 cells. The ROS level in H322M cells was increased after PDTC treatment, and pretreatment with N-acetyl-cysteine (NAC) reversed PDTC-induced ACE2 suppression. Meanwhile, treatment with hydrogen peroxide augmented ACE2 suppression in H322M cells with p50 knockdown. Two repurposed NF-κB inhibitors, the anthelmintic drug triclabendazole and the antiprotozoal drug emetine, also reduced ACE2 mRNA and protein levels. Moreover, zinc supplementation augmented the suppressive effects of triclabendazole and emetine on ACE2 expression in H322M and Calu-3 cells. SIGNIFICANCE: These results suggest that ACE2 expression is modulated by ROS and NF-κB signaling in human lung cells, and the combination of zinc with triclabendazole or emetine shows promise for clinical treatment of ACE2-related disease.


Subject(s)
Angiotensin-Converting Enzyme 2/genetics , Antiparasitic Agents/pharmacology , Down-Regulation/drug effects , Emetine/pharmacology , NF-kappa B/antagonists & inhibitors , Triclabendazole/pharmacology , Zinc/pharmacology , COVID-19/drug therapy , COVID-19/genetics , Cell Line , Drug Repositioning , Humans , Lung/cytology , Lung/drug effects , Lung/metabolism , Pyrrolidines/pharmacology , Thiocarbamates/pharmacology
13.
Virol J ; 18(1): 113, 2021 06 03.
Article in English | MEDLINE | ID: covidwho-1279301

ABSTRACT

BACKGROUND: Respiratory RNA viruses including influenza virus have been a cause of health and economic hardships. These viruses depend on its host for replication and infection. Influenza virus infection is lethal to the chick embryo. We examined whether a combination of trimethoprim and zinc (Tri-Z), that acts on the host, can reduce the lethal effect of influenza A virus in chick embryo model. METHOD: Influenza virus was isolated from patients and propagated in eggs. We determined viral load that infects 50% of eggs (50% egg lethal dose, ELD50). We introduced 10 ELD50 into embryonated eggs and repeated the experiments using 100 ELD50. A mixture of zinc oxide (Zn) and trimethoprim (TMP) (weight/weight ratios ranged from 0.01 to 0.3, Zn/TMP with increment of 0.1) was tested for embryo survival of the infection (n = 12 per ratio, in triplicates). Embryo survival was determined by candling eggs daily for 7 days. Controls of Zn, TMP, saline or convalescent serum were conducted in parallel. The effect of Tri-Z on virus binding to its cell surface receptor was evaluated in a hemagglutination inhibition (HAI) assay using chicken red cells. Tri-Z was prepared to concentration of 10 mg TMP and 1.8 mg Zn per ml, then serial dilutions were made. HAI effect was expressed as scores where ++++ = no effect; 0 = complete HAI effect. RESULTS: TMP, Zn or saline separately had no effect on embryo survival, none of the embryos survived influenza virus infection. All embryos treated with convalescent serum survived. Tri-Z, at ratio range of 0.15-0.2 (optimal ratio of 0.18) Zn/TMP, enabled embryos to survive influenza virus despite increasing viral load (> 80% survival at optimal ratio). At concentration of 15 µg/ml of optimal ratio, Tri-Z had total HAI effect (scored 0). However, at clinical concentration of 5 µg/ml, Tri-Z had partial HAI effect (+ +). CONCLUSION: Acting on host cells, Tri-Z at optimal ratio can reduce the lethal effect of influenza A virus in chick embryo. Tri-Z has HAI effect. These findings suggest that combination of trimethoprim and zinc at optimal ratio can be provided as treatment for influenza and possibly other respiratory RNA viruses infection in man.


Subject(s)
Influenza A virus , Orthomyxoviridae Infections , Trimethoprim/pharmacology , Zinc/pharmacology , Animals , Chick Embryo , Humans , Orthomyxoviridae Infections/drug therapy
14.
Nutr Res ; 92: 109-128, 2021 08.
Article in English | MEDLINE | ID: covidwho-1267875

ABSTRACT

Novel coronavirus disease 2019 (COVID-19) has spread across the globe; and surprisingly, no potentially protective or therapeutic antiviral molecules are available to treat severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) infection. However, zinc (Zn) and copper (Cu) have been shown to exert protective effects due to their antioxidant, anti-inflammatory, and antiviral properties. Therefore, it is hypothesized that supplementation with Zn and Cu alone or as an adjuvant may be beneficial with promising efficacy and a favorable safety profile to mitigate symptoms, as well as halt progression of the severe form of SARS-CoV-2 infection. The objective of this review is to discuss the proposed underlying molecular mechanisms and their implications for combating SARS-CoV-2 infection in response to Zn and Cu administration. Several clinical trials have also included the use of Zn as an adjuvant therapy with dietary regimens/antiviral drugs against COVID-19 infection. Overall, this review summarizes that nutritional intervention with Zn and Cu may offer an alternative treatment strategy by eliciting their virucidal effects through several fundamental molecular cascades, such as, modulation of immune responses, redox signaling, autophagy, and obstruction of viral entry and genome replication during SARS-CoV-2 infection.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Copper/pharmacology , Trace Elements/pharmacology , Zinc/pharmacology , Anti-Inflammatory Agents/pharmacology , Antioxidants/pharmacology , Humans , SARS-CoV-2
16.
Int Immunopharmacol ; 96: 107630, 2021 Jul.
Article in English | MEDLINE | ID: covidwho-1163925

ABSTRACT

The novel SARS-CoV-2 which was first reported in China is the cause of infection known as COVID-19. In comparison with other coronaviruses such as SARS-CoV and MERS, the mortality rate of SARS-CoV-2 is lower but the transmissibility is higher. Immune dysregulation is the most common feature of the immunopathogenesis of COVID-19 that leads to hyperinflammation. Micronutrients such as zinc are essential for normal immune function. According to the assessment of WHO, approximately one-third of the world's society suffer from zinc deficiency. Low plasma levels of zinc are associated with abnormal immune system functions such as impaired chemotaxis of polymorphonuclear cells (PMNs) and phagocytosis, dysregulated intracellular killing, overexpression of the inflammatory cytokines, lymphopenia, decreased antibody production, and sensitivity to microbes especially viral respiratory infections. Zinc exerts numerous direct and indirect effects against a wide variety of viral species particularly RNA viruses. The use of zinc and a combination of zinc-pyrithione at low concentrations impede SARS-CoV replication in vitro. Accordingly, zinc can inhibit the elongation step of RNA transcription. Furthermore, zinc might improve antiviral immunity by up-regulation of IFNα through JAK/STAT1 signaling pathway in leukocytes. On the other hand, zinc supplementation might ameliorate tissue damage caused by mechanical ventilation in critical COVID-19 patients. Finally, zinc might be used in combination with antiviral medications for the management of COVID-19 patients. In the current review article, we review and discuss the immunobiological roles and antiviral properties as well as the therapeutic application of zinc in SARS-CoV-2 and related coronaviruses infections.


Subject(s)
COVID-19/pathology , SARS-CoV-2/drug effects , Zinc/metabolism , Zinc/pharmacology , Humans , Virus Replication/drug effects
17.
Clin Nutr ESPEN ; 43: 39-48, 2021 06.
Article in English | MEDLINE | ID: covidwho-1157201

ABSTRACT

BACKGROUND: The enormous health impact of the COVID-19 pandemic has refocused attention on measures to optimize immune function and vaccine response. Dietary deficiencies of micronutrients can weaken adaptive immunity. The aim of this review was to examine links between micronutrients, immune function and COVID-19 infection, with a focus on nutritional risks in subgroups of the Swiss population. METHODS: Scoping review on the associations between selected micronutrients (vitamins D and C, iron, selenium, zinc, and n-3 PUFAs) and immunity, with particular reference to the Swiss population. These nutrients were chosen because previous EFSA reviews have concluded they play a key role in immunity. RESULTS: The review discusses the available knowledge on links between sufficient nutrient status, optimal immune function, and prevention of respiratory tract infections. Because of the rapid spread of the COVID-19 pandemic, controlled intervention studies of micronutrients in the context of COVID-19 infection are now underway, but evidence is not yet available to draw conclusions. The anti-inflammatory properties of n-3 PUFAs are well established. In Switzerland, several subgroups of the population are at clear risk of nutrient deficiencies; e.g., older adults, multiple comorbidities, obesity, pregnancy, and institutionalized. Low intakes of n-3 PUFA are present in a large proportion of the population. CONCLUSION: There are clear and strong relationships between micronutrient and n-3 PUFA status and immune function, and subgroups of the Swiss population are at risk for deficient intakes. Therefore, during the COVID-19 pandemic, as a complement to a healthy and balanced diet, it may be prudent to consider supplementation with a combination of moderate doses of Vitamins C and D, as well as of Se, Zn and n-3 PUFA, in risk groups.


Subject(s)
COVID-19/drug therapy , Dietary Supplements , Fatty Acids, Omega-3/therapeutic use , Immunologic Factors/therapeutic use , Trace Elements/therapeutic use , Vitamins/therapeutic use , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use , Ascorbic Acid/pharmacology , Ascorbic Acid/therapeutic use , COVID-19/immunology , Comorbidity , Fatty Acids, Omega-3/pharmacology , Female , Humans , Immunologic Factors/pharmacology , Male , Micronutrients/pharmacology , Micronutrients/therapeutic use , Nutritional Status , Pandemics , Pregnancy , SARS-CoV-2 , Selenium/pharmacology , Selenium/therapeutic use , Switzerland , Trace Elements/pharmacology , Vitamin D/pharmacology , Vitamin D/therapeutic use , Vitamins/pharmacology , Zinc/pharmacology , Zinc/therapeutic use
18.
Int J Mol Sci ; 22(4)2021 Feb 16.
Article in English | MEDLINE | ID: covidwho-1085070

ABSTRACT

The novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2/COVID-19), is a worldwide pandemic, as declared by the World Health Organization (WHO). It is a respiratory virus that infects people of all ages. Although it may present with mild to no symptoms in most patients, those who are older, immunocompromised, or with multiple comorbidities may present with severe and life-threatening infections. Throughout history, nutraceuticals, such as a variety of phytochemicals from medicinal plants and dietary supplements, have been used as adjunct therapies for many disease conditions, including viral infections. Appropriate use of these adjunct therapies with antiviral proprieties may be beneficial in the treatment and/or prophylaxis of COVID-19. In this review, we provide a comprehensive summary of nutraceuticals, such as vitamins C, D, E, zinc, melatonin, and other phytochemicals and function foods. These nutraceuticals may have potential therapeutic efficacies in fighting the threat of the SARS-CoV-2/COVID-19 pandemic.


Subject(s)
COVID-19/drug therapy , Dietary Supplements , Melatonin/therapeutic use , Vitamins/therapeutic use , Zinc/therapeutic use , Animals , Antiviral Agents/pharmacology , Antiviral Agents/therapeutic use , Ascorbic Acid/pharmacology , Ascorbic Acid/therapeutic use , Dietary Supplements/analysis , Functional Food/analysis , Humans , Melatonin/pharmacology , SARS-CoV-2/drug effects , Vitamin D/pharmacology , Vitamin D/therapeutic use , Vitamin E/pharmacology , Vitamin E/therapeutic use , Vitamins/pharmacology , Zinc/pharmacology
19.
Nutrients ; 13(2)2021 Feb 09.
Article in English | MEDLINE | ID: covidwho-1069852

ABSTRACT

BACKGROUND: Zinc is an essential micronutrient that impacts host-pathogen interplay at infection. Zinc balances immune responses, and also has a proven direct antiviral action against some viruses. Importantly, zinc deficiency (ZD) is a common condition in elderly and individuals with chronic diseases, two groups with an increased risk for severe severe coronavirus disease 2019 (COVID-19) outcomes. We hypothesize that serum zinc content (SZC) influences COVID-19 disease progression, and thus might represent a useful biomarker. METHODS: We ran an observational cohort study with 249 COVID-19 patients admitted in Hospital del Mar. We have studied COVID-19 severity and progression attending to SZC at admission. In parallel, we have studied severe acute respiratory syndrome coronavirus 2 (SARS-CoV2) replication in the Vero E6 cell line modifying zinc concentrations. FINDINGS: Our study demonstrates a correlation between serum zinc levels and COVID-19 outcome. Serum zinc levels lower than 50 µg/dL at admission correlated with worse clinical presentation, longer time to reach stability, and higher mortality. Our in vitro results indicate that low zinc levels favor viral expansion in SARS-CoV-2 infected cells. INTERPRETATION: Low SZC is a risk factor that determines COVID-19 outcome. We encourage performing randomized clinical trials to study zinc supplementation as potential prophylaxis and treatment with people at risk of zinc deficiency.


Subject(s)
COVID-19/blood , COVID-19/pathology , SARS-CoV-2 , Zinc/blood , Aged , Animals , Cell Survival , Chlorocebus aethiops , Cohort Studies , Female , Humans , Male , Middle Aged , Vero Cells , Zinc/administration & dosage , Zinc/pharmacology
20.
Int J Mol Med ; 47(3)2021 03.
Article in English | MEDLINE | ID: covidwho-1067805

ABSTRACT

Coronavirus disease 2019 (COVID­19), caused by severe acute respiratory syndrome coronavirus 2 (SARS­CoV­2), was identified in December, 2019 in Wuhan, China. Since then, it has continued to spread rapidly in numerous countries, while the search for effective therapeutic options persists. Coronaviruses, including SARS­CoV­2, are known to suppress and evade the antiviral responses of the host organism mediated by interferon (IFN), a family of cytokines that plays an important role in antiviral defenses associated with innate immunity, and has been used therapeutically for chronic viral diseases and cancer. On the other hand, OncoTherad, a safe and effective immunotherapeutic agent in the treatment of non­muscle invasive bladder cancer (NMIBC), increases IFN signaling and has been shown to be a promising therapeutic approach for COVID­19 in a case report that described the rapid recovery of a 78­year­old patient with NMIBC with comorbidities. The present review discusses the possible synergistic action of OncoTherad with vitamin D, zinc and glutamine, nutrients that have been shown to facilitate immune responses mediated by IFN signaling, as well as the potential of this combination as a therapeutic option for COVID­19.


Subject(s)
Antiviral Agents/pharmacology , COVID-19/drug therapy , Glutamine/pharmacology , Glycoproteins/pharmacology , Immunologic Factors/therapeutic use , Interferons/metabolism , Phosphates/pharmacology , Vitamin D/pharmacology , Zinc/pharmacology , Aged , Antiviral Agents/therapeutic use , COVID-19/metabolism , Comorbidity , Drug Synergism , Glycoproteins/therapeutic use , Humans , Immunity, Innate/drug effects , Immunologic Factors/pharmacology , Male , Nanostructures , Phosphates/therapeutic use , Urinary Bladder Calculi/drug therapy , Urinary Bladder Calculi/epidemiology
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