Immunomodulatory Effects of Zinc as a Supportive Strategies for COVID-19

Main Article Content

Nahla A. Tayyib
Pushpamala Ramaiah
Fatmah J. Alsolami
Mohammed S. Alshmemri

Abstract

Coronaviruses 2019 (Covid-19) is a massive family of viruses that causes respiratory illnesses ranging from the common cold to the most severe conditions such as Middle East Respiratory Syndrome and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) that represents the humanitarian crisis on a global scale. Currently, there are no therapeutic strategies approved by the U.S.Food and Drug Administration (FDA) to cure or prevent COVID-19. Global research efforts from around the world extrapolate the updates focusing specifically on the biphasic nature of Covid-19 that involve both innate and acquired immunity. Even though researchers around the globe are racing to invent a life-saving therapeutics and vaccines to tackle COVID-19, the only available venture is a supportive approach in rendering treatment to patients with severe and non-severe cases of COVID-19. Supplementation of several vitamins and trace elements showed the expected favorable impact on enhancing immunity in viral infection. Numerous studies prompted the value of zinc (Zn) supplementation that prevents the virus from entering cells by binding with protein in potentiating antiviral immunity, which is realized through different mechanisms, including the improvement in markers of immune function. Zinc is also an associated factor for several enzymes (needed for the activity for over 300 enzymes), transcription factors, and replication factors. Interestingly, low-level zinc results in dysfunction of all immune cells, subjects with altered zinc state have a high risk for infectious disorders, autoimmune disorders, and cancer. Several assumptions regarding immunomodulators of zinc remain unresolved. This review aimed to explore the hypothetical association of Zinc supplementation (the key immunomodulator) in association with a preventive and therapeutic role of treating patients with COVID-19.

Keywords:
Immunomodulator, zinc supplementation, supportive strategies, innate immunity, acquired immunity, COVID-19.

Article Details

How to Cite
Tayyib, N. A., Ramaiah, P., Alsolami, F. J., & Alshmemri, M. S. (2020). Immunomodulatory Effects of Zinc as a Supportive Strategies for COVID-19. Journal of Pharmaceutical Research International, 32(13), 14-22. https://doi.org/10.9734/jpri/2020/v32i1330577
Section
Review Article

References

John Hopkins University and Medicine. Coronavirus resource center.

Available:https://coronavirus.jhu.edu/map.html

Accessed on 5-07-2020

Science News.

Available:https://www.sciencenews.org/article/covid-19-coronavirus-sense-smell-brain-nerve-cells.

Accessed July 2, 2020

Kumar A, Kubota Y, Chernov M, Kasuya H. Potential role of zinc supplementation in prophylaxis and treatment of COVID-19. Med Hypotheses. 2020;144:109848.

DOI: 10.1016/j.mehy.2020.109848

Epub ahead of print.

PMID: 32512490; PMCID: PMC7247509.

People who are at increased risk for severe illness. National Center-forImmunization and Respiratory Diseases (NCIRD).

Available:https://www.cdc.gov/coronavirus/2019-ncov/need-extra-precautions/people-at-increased-risk.html

Morawska L, Cao J. Airborne transmission of SARS CoV2: The world should face the reality. Env Int. 2020;139.

Available:https://doi.org/10.1016/j.envint.2020.105730

Prasad AS. Discovery of zinc for human health and biomarkers of zinc deficiency: Molecular, genetic and nutritional aspects of major and trace minerals. Collins JF. Academic Press. Cambridge. 2017;241-260.

Krezel A, Maret W. The functions of metamorphic Mettallotheolleins in Zinc and Copper metabolism. Int J of Mol Sci. 2017;18:1237.

Haase H, Rink L. Zinc signals and immune function. Biofactors. 2014;40(1):27-40.

DOI:10.1002/biof.1114

Hojyo S, Fukada T. Role of Zinc signaling in the immune system. Journal of Immunology Research;2016.

Available:https://doi.org/10.1155/2016/6762343

Skalny AV, Rink L, Ajsuvakova OP, Aschner M, Gritsenko VA, Alekseenko SI. Zinc and respiratory tract infection: Perspectives for Covid-19 (Review). International Journal of Molecular Medicine. 2020;46:17-26.

Bonaventura P,Benedetti G, Alberede F, Mossec P. Zinc and its role in immunity and inflammation. Autoimmun Rev. 2015;14:277-285.

Guastalegname M, Vallone A. Could Chloroquine/Hydroxychloroquine be harmful in Coronavirus disease 2019 (COVID-19) treatment?.Clin Infect Dis.; 2020.

Dabbagh BH, Clergeaud G, Quesada IM, O’Sullivan CK, Fernandez-Larrea JB. Zinc ionophore activity of quercetin and epigallocatechin-gallate: From Hepa 1-6 cells to a liposome model.J Agric Food Chem. 2014;62:8085-8093.

Xue J, Moyer A, Peng B, Wu J, Hannafon BN, Ding WQ. Choloroquine is a zinc ionophore. PLoS One. 2014;9(10).

Weintraub K. Chloroquine zinc trails underway for Covid-19 prophylaxis; 2020.

Available:https://www.medscape.com/viewarticle/928472

Hemilä H, Chalker E. The effectiveness of high dose zinc acetate lozenges on various common cold symptoms: Ameta-analysis. BMC FamPract.2015; 16(24).

Available:https://doi.org/10.1186/s12875-015-0237-6

Wessels I, Maywald M, Rink L. Zinc as a gatekeeper of immune function. Nutrients. 2017;9(12):1286.

DOI:10.3390/nu9121286

Boudreault F, Pinilla-Vera M, Englert JA, Kho AT, Isabelle C, et al. Zinc deficiency prime the lung for ventilator-induced injury. Africa Insight. 2017;2(11).

Chen X, Bian J, Ge Y. Zinc- deficient diet aggravates ventilation-induced lung injury in rats. J Biomed. 2012;26:59-65.

Pooja S, Damian H. Does zinc improve symptoms of viral upper respiratory tract infection? Evid based Pr. 2020;23(1):37-39.

Waqas N, Khan SA, Nahed A, Sheikh ZI. Efficacy of oral zinc sulphate in the treatment of recalcitrate common warts. J of Rawalpindi Medical College. 2017; 21(3):245-247.

Matsumura H, Nirei K, Nakamura H, Arakawa Y, Higuchi T, Hayashi J, et al. Zinc supplementation therapy improves the outcome of patients with chronic hepatitis C. J ClinBiochemNutrin. 2012;51(3):178-184.

Ahmed NJ. Chloroquine and Hydroxy-chloroquinecould be an available weapons to treat Covid-19 associated Pneumonia. J Pharm Res Int. 2020;32(9):52-60.

Ahmed SA, Mahran SA, RiyadhSA, Abir SM, Khalid AA, Abdelbabgi EF, et al. Optimizing the use of Hydroxychloroquine in the management of COVID-19 given its pharmacological profile. J Pharm Res Int. 2020;32(8):29-43.

Sun P, Qie S, Liu Z, Ren J, Xi JJ. Clinical characteristics of 50466 patients with 2019 nCoV infection. Med Rxiv; 2020.

Read SA, Obeid S, Ahlenstiel C, Ahlenstiel G. The ole of zinc in antiviral immunity. AdvNutr. 2019;10:669-710.

Velthuis AJW, Van Den Worm SHE, Sims AC, Baric RS, Snijdir EJ, Van Hemrt MJ. PloSPathog. 2010:6.

Available:https://www.ema.europa.eu/en/news/covid-19-chloroquine-hydroxychloroquine-only-be-used-clinical-trials-emergency-use-programmes

Derwand R, Scholtz M. Does zinc supplementation enhance the clinical efficacy of Chloroquine/Hydrochloroquine to win today’s battles against Covid-19? Med Hypotheses. 2020;142.

Grossman NYU. Zinc-hydroxychloroquine found effective in some COVID-19 patients: Study. France 24; 2020.

Available:https://www.france24.com/en/20200511-zinc-hydroxychloroquine-found-effective-in-some-covid-19-patients-study

Soltani S, Zakeri AM, Karimi MR, Rezayat SA, Anbaji FZ, Tabibzadeh A, et al. A systematic literature review of current therapeutic approaches for Covid-19 patients. J Pharm Res Int. 2020;32(7):13-25.

Sing S, Sing RK. Assessing the role of zinc in COVID-19 infections and mortality: Is zinc deficiency a risk factor for COVID-19. Med RXiv and Bio Rxiv; 2020. Preprint

Bailey RL, West KP, Black RE. The epidemiology of global micronutrient deficiencies. Ann NutrMetab. 2015;9:22-33.

Yasuda H, Tsutsui T. Infants and elderlies are susceptible to zinc deficiency. Sci Rep. 2016;6:21850.

Bhat MH, Rather AB, Dhobi GN, Koul AN, Bhat FA, Hussain A. Zinc levels in community acquired pneumonia in hospitalized patients: A case control study. Egypt J Chest Dis Tuberc. 2016;65:485-489.

Gammoh NZ, Rink L. Zinc and the Immune system. Nutrition and Immunity. 2019:127-158.

Bao B, Prasad AS, Beck FW, Fitzgerald JT, Snell D, Bao GW, et al. Zinc decreases C-reactive protein, lipid peroxidation, and anti-inflammatory cytokines in elderly subjects: A potential implication of zinc as an atheroprotective agent. 2010;91(6):1634.

Lin MH, Moses DC, Hsieh CH, Cheng SC, Cheng YH, Sun CY, et al. Disulphiram can inhibit MERS and SARS coronavirus papain like protease via different modes. Antiviral Res. 2018;150:155-163.

Dave VK, Hylton CA. BMJ. 2020;368:m864.

Rerksuppaphol S, Rerksuppaphol L. A randomized control trial of zinc supplementation in the treatment of acute respiratory tract infection in Thai children. Pediatr Res. 2019;11(2):7954.

Sun Q, van Dam RM, Willet WC, Hu FB. Prospective study of zinc intake and risk of type 2 diabetes in women. Diabetes care. 2009;32(4):629-34.

Qasemzadeh MJ, Fathi M, Tashvighi M, Garehbeglou M, Damavandi SY, Pasa Y, et al. The effect of adjuvant zinc therapy on recovery from pneumonia in hospitalized children: A double blind randamized control trial. Scientifica; 2014.

Todd Neff. Coronavirus: To zinc or not to zinc? UC Health Today.

Available:https://www.uchealth.org/today/zinc-could-help-diminish-extent-of-covid-19/

Accessed on 6/07/2020

Prasad AS.Discovery of human zinc deficiency: Its impact on human health and disease.AdvNutr. 2013;492:176-90

Das S. Zinc can play pertinent role in mitigating Covid-19. ET Health World.com. May 7; 2020.

Sinha N, Balayla G. Hydrochloroquine and Covid-19. Postgraduate Med Journal; 2020.

Bhardwaj SS, Alduwayhi S, Bhardwaj A. COVID-19 various treatment options and special considerations for dentistry. J Pharm Res Int. 2020;32(10):70-76.

Bae SN, Lee KH, Kim JH, Lee SJ, Park LO. Zinc induces apoptosis on cervical carcinoma cells by p53 dependent and independent pathways. BiochemBiophys Res Commun. 2017;484;1:218-23.

Shamanna RA, Hoque M, Pe’ery T, Mathews MB. Induction of p53,p21, and apoptosis by silencing the NF90/NF45 (Nuclear factor) complex in human papilloma virus-transformed cervical carcinoma cells. Oncogene. 2013;32(43): 5176-85.

Ghaffari H, Tavakoli A, Moradi A, Tabarraei A, Salim FB, Zahmatkeshan M, et al. Inhibition of H1N1 influenza virus infection by zinc oxide nanoparticles: Another emerging application of nanomedicine. J Biomed Sci. 2019;26:90.

Siddiqi KS, Rahman A, Husen A. Properties of zinc oxide nanoparticles and their activity against microbes. Nanoscale Res Lett. 2018;13(1):141.

Tavakoli A, Ataei-Pirkooh A, Mm Sadeghi G,Bokharaei-Salim F, Sahrapour P, KianiSH, et al. Polyethylene glycol-coated zinc oxide nanoparticles: An efficient nanoweapon to fight against herpes simplex virus type 1.Nanomedicine. 2018; 13(21):2675-90.

Walraven CV, Rodic S, McCudden C. Factors associated with zinc levels inhospitalizedpatients:An observational study using routinely collected data. J TraceElem Med Bio. 2020;61.