Evaluation the plausibility of pepurpose of levamisole and niclosamide in treatment of Covid-19

Year 2022, Volume: 3 Issue: 1, 30 - 36, 01.12.2022

Ahmed Badri Abed , Safiye Elif Korcan

https://doi.org/10.37662/jpt.2022.999481

Abstract

Since the world health organization declared the pandemic of covid 19, many drugs have been tested and re-evaluated to find effective treatment for the novel corona virus infection. Niclosamide and Levamisole which are FDA approved anthelmintic drugs have been evaluated by many researchers and agencies to repurpose of these drugs as additional options for existing treatment strategy used for patients with Covid-19. Hence we are trying in this review to introduce most reports that evaluated the use of Niclosamide and Levamisole for treatment of patients infected with Covid 19 .We concluded that the encouraging studies regarding the repurpose of the two drugs may highlighting for further studies that can widening the options for existing treatment strategy used for patients with COVID-19.

Keywords

Covid 19, Levamisole, Niclosamide

References

• [1] WHO Expert Committee on the Selection, Use of Essential Medicines, World Health Organization. The selection and use of essential medicines. World Health Organization; 2008.
• [2] Chen W, Mook RA, Premont RT, Wang J. Niclosamide: Beyond an antihelminthic drug. Cellular Signalling. 2018;41:89-96.
• [3] Pindiprolu SH, Pindiprolu SKS. CD133 receptor mediated delivery of STAT3 inhibitor for simultaneous elimination of cancer cells and cancer stem cells in oral squamous cell carcinoma. Medical Hypotheses. 2019;129:109241.
• [4] Pan J, Ding K, Wang C. Niclosamide, an old antihelminthic agent, demonstrates antitumor activity by blocking multiple signaling pathways of cancer stem cells. Chin J Cancer. 2012;31(4):178-84.
• [5] Presidente PJ, Worley DE. Efficacy of levo-tetramisole against experimental Dictyocaulusfilaria in lambs. American journal of veterinary research. 1969;30(9):1625-30.
• [6] Gatti F, Krubwa F, Vandepitte J, Thienpont D. Control of intestinal nematodes in African schoolchildren by the trimestrial administration of levamisole. Ann SocBelg Med Trop. 1972;52(1):19-31.
• [7] Thienpont D. Tetramisole (R 8299), a new, potent broad spectrum anthelmintic. Nature. 1966;209:1084-6.
• [8] Thienpont D, Brugmans J, Abadi K, Tanamal S. Tetramisole in the treatment of nematode infections in man. The American journal of tropical medicine and hygiene. 1969;18(4):520-5.
• [9] Lee KC, Ladizinski B, Federman DG. Complications Associated With Use of Levamisole-Contaminated Cocaine: An Emerging Public Health Challenge. Mayo Clinic Proceedings. 2012;87(6):581-6.
• [10] Scheinfeld N, Rosenberg JD, Weinberg JM. Levamisole in Dermatology. American Journal of Clinical Dermatology. 2004;5(2):97-104.
• [11] U.S. Food and Drug Administration. FDA approval: Levamisole https://www.accessdata.fda.gov/scripts/cder/daf/index.cfm?event=overview.process&ApplNo=020035
• [12] Yin J, Jin H, Yang F, et al. Synergistic effects of adjuvants interferon-gamma and levamisole on DNA vaccination against infection with Newcastle disease virus. Viral Immunol. 2007;20(2):288-99.
• [13] Singh KCP, Dhawedkar RG. Immunomodulating effects of levamisole in chicks immunocompromised by infectious bursal disease virus. Trop Anim Health Prod. 1993;25(1):11-4.
• [14] Giambrone JJ, Klesius PH. Effect of levamisole on the response of broilers to coccidiosis vaccination. Poult Sci. 1985;64(6):1083-9.
• [15] Weinbach EC, GARBUS J. Mechanism of action of reagents that uncouple oxidative phosphorylation. Nature. 1969 Mar;221(5185):1016-8.
• [16] Wang J, Ren X, Piao H, et al. Niclosamide-induced Wnt signaling inhibition in colorectal cancer is mediated by autophagy. Biochemical Journal. 2019;476(3):535-46.
• [17] Tomizawa M, Shinozaki F, Motoyoshi Y, et al. Niclosamide suppresses hepatoma cell proliferation via the Wnt pathway. OTT. 2013 ;6:1685–1693.
• [18] Andersen PI, Krpina K, Ianevski A, et al. Novel Antiviral Activities of Obatoclax, Emetine, Niclosamide, Brequinar, and Homoharringtonine. Viruses. 2019;11(10):E964.
• [19] Kao J, HuangFu W, Tsai T, et al. The antiparasitic drug niclosamide inhibits dengue virus infection by interfering with endosomal acidification independent of mTOR. PLoSNegl Trop Dis. 2018;12(8):e0006715.
• [20] Jurgeit A, McDowell R, Moese S, Meldrum E, Schwendener R, Greber UF. Niclosamide Is a Proton Carrier and Targets Acidic Endosomes with Broad Antiviral Effects. PLoSPathog. 2012;8(10):e1002976.
• [21] Jung E, Nam S, Oh H, et al. Neutralization of Acidic Intracellular Vesicles by Niclosamide Inhibits Multiple Steps of the Dengue Virus Life Cycle In Vitro. Sci Rep. 2019;9(1): 1-2.
• [22] Li Z, Brecher M, Deng Y, et al. Existing drugs as broad-spectrum and potent inhibitors for Zika virus by targeting NS2B-NS3 interaction. Cell Res. 2017;27(8):1046-64.
• [23] Xu M, Lee EM, Wen Z, et al. Identification of small-molecule inhibitors of Zika virus infection and induced neural cell death via a drug repurposing screen. Nat Med. 2016;22(10):1101-7.
• [24] Cairns DM, Boorgu DSSK, Levin M, Kaplan DL. Niclosamide rescues microcephaly in a humanized in vivo model of Zika infection using human induced neural stem cells. Biology Open. 2018;7(1):bio031807.
• [25] Wang Y, Lu J, Lin C, et al. Antiviral activities of niclosamide and nitazoxanide against chikungunya virus entry and transmission. Antiviral Research. 2016;135:81-90.
• [26] Hulseberg CE, Fénéant L, Szymańska-de Wijs KM, et al. Arbidol and Other Low-Molecular-Weight Drugs That Inhibit Lassa and Ebola Viruses. J Virol. 2019;93(8):
• [27] Huang L, Yang M, Yuan Y, Li X, Kuang E. Niclosamide inhibits lytic replication of Epstein-Barr virus by disrupting mTOR activation. Antiviral Research. 2017;138:68-78.
• [28] Fang J, Sun L, Peng G, et al. Identification of Three Antiviral Inhibitors against Japanese Encephalitis Virus from Library of Pharmacologically Active Compounds 1280. PLoS ONE. 2013;8(11):e78425.
• [29] Wu C, Jan J, Chen C, et al. Inhibition of Severe Acute Respiratory Syndrome Coronavirus Replication by Niclosamide. AAC. 2004;48(7):2693-6.
• [30] Wen C, Kuo Y, Jan J, et al. Specific Plant Terpenoids and Lignoids Possess Potent Antiviral Activities against Severe Acute Respiratory Syndrome Coronavirus. J Med Chem. 2007;50(17):4087-95.
• [31] Shie J, Fang J, Kuo C, et al. Discovery of Potent Anilide Inhibitors against the Severe Acute Respiratory Syndrome 3CL Protease. J Med Chem. 2005;48(13):4469-73.
• [32] Gassen NC, Niemeyer D, Muth D, et al. SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection. Nat Commun. 2019;10(1): 1-6.
• [33] Zhou P, Yang X, Wang X, et al. A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature. 2020;579(7798):270-3.
• [34] Xu J, Shi P, Li H, Zhou J. Broad Spectrum Antiviral Agent Niclosamide and Its Therapeutic Potential. ACS Infect Dis. 2020;6(5):909-15.
• [35] Pindiprolu SKS, Pindiprolu SH. Plausible mechanisms of Niclosamide as an antiviral agent against COVID-19. Medical Hypotheses. 2020;140:109765.
• [36] The University of Texas . New Delivery Method Could Make Niclosamide an Effective Antiviral to Treat COVID-19.2020. available at:https://news.utexas.edu/2020/04/06/new-delivery-method-could-make-niclosamide-an-effective-antiviral-to-treat-covid-19/
• [37] Brunaugh AD, Seo H, Warnken Z, Ding L, Seo SH, Smyth HD. Broad-spectrum, patient-adaptable inhaled niclosamide-lysozyme particles are efficacious against coronaviruses in lethal murine infection models. bioRxiv. 2020 Jan 1.
• [38] Wang G, Gaikwad H, McCarthy M, et al. Lipid nanoparticle formulation of niclosamide (nano NCM) effectively inhibits SARS-CoV-2 replication in vitro. Precision Nanomedicine. 2021;4(1):724-37.
• [39] Tufts Medical Center .Niclosamide for Mild to Moderate COVID-19 2020 . Available at: https://clinicaltrials.gov/ct2/show/NCT04399356.
• [40] Prabhakara C, Godbole R, Sil P, Jahnavi S, van Zanten TS, Sheth D, Subhash N, Chandra A, Nuthakki VK, Puthiyapurayil TP, Ahmed R. Niclosamide inhibits SARS-CoV2 entry by blocking internalization through pH-dependent CLIC/GEEC endocytic pathway. bioRxiv. 2020 Jan 1.
• [41] BioSpectrum Asia. Mankind, Daewoong Pharma to use Niclosamide for COVID-19 treatment. Available at: https://www.biospectrumasia.com/news/25/16498/mankind-daewoong-pharma-to-use-niclosamide-for-covid-19-treatment.html
• [42] Drugbank. Levamisole.https://www.drugbank.ca/drugs/DB00848.
• [43] Goldstein G. Mode of action of levamisole. The Journal of rheumatology. Supplement. 1978;4:143-8.
• [44] Fischer GW, Podgore JK, Bass JW, Kelley JL, Kobayashi GY. Enhanced Host Defense Mechanisms with Levamisole in Suckling Rats. Journal of Infectious Diseases. 1975;132(5):578-81.
• [45] Obrosova-Serova NP, Schastnyĭ EI, Kupriashina LM, Slepushkin AN, Shenderovich SF. Immunomodulating action of levamisole in its combined use with influenza vaccines. Voprosyvirusologii. 1984;29(4):454-9.
• [46] Pike MC, Daniels CA, Snyderman R. Influenza-induced depression of monocyte chemotaxis: Reversal by levamisole. Cellular Immunology. 1977;32(1):234-8.
• [47] Symoens J, Rosenthal M. Levamisole in the modulation of the immune response: the current experimental and clinical state. J Reticuloendothel Soc. 1977;21(3):175-221.
• [48] Szeto C, Gillespie KM, Mathieson PW. Levamisole induces interleukin-18 and shifts type 1/type 2 cytokine balance. Immunology. 2000;100(2):217-24.
• [49] Wang K. Effect of liniment levamisole on cellular immune functions of patients with chronic hepatitis B. WJG. 2005;11(45):7208.
• [50] Demirci F, Bayraktaroğlu Z, Karaoğlan M, Coşkun Y, Karaoğlan I, Okan V. Immunomodulatory effects of HBsAg vaccine and levamisole in chronic hepatitis B and hepatitis B carrier children. Turk J Gastroenterol. 2005;16(4):188-93.
• [51] Karaoglan M, Demirci F, Coskun Y, et al. Immunomodulation therapy in children with chronic hepatitis B. J Natl Med Assoc. 2006;98(2):143-7.
• [52] Yin J, Jin H, Kang Y, et al. Efficacy of Modified Levamisole Adjuvant on Inactivated Virus Vaccine. Viral Immunology. 2006;19(3):525-35.
• [53] Kang Y, Jin H, Zheng G, et al. The adjuvant effect of levamisole on killed viral vaccines. Vaccine. 2005;23(48-49):5543-50.
• [54] Grishchenko SV, Lavrukhina LA, Ketiladze ES, Krylov VF, Ershov FI. [Results of combined therapy using levamisole for patients with influenza complicated by pneumonia].VoprVirusol. 1984;29(2):175-9.
• [55] Shomali T, Mosleh N, Alaeddini A. Levamisole enhances cell-mediated immune responses and reduces shedding of H9N2 avian influenza virus in Japanese quails (Coturnixcoturnix japonica). American Journal of Animal and Veterinary Sciences. 2012;7(1):16-20.
• [56] Uyaroğlu OA, Güven GS, Güllü İ. Can Levamisole be used in the treatment of COVID-19 patients presenting with diarrhea?.J Infect DevCtries. 2020;14(08):844-6.
• [57] Roostaei Firozabad A, Meybodi ZA, Mousavinasab SR, et al. Efficacy and safety of Levamisole treatment in clinical presentations of non-hospitalized patients with COVID-19: a double-blind, randomized, controlled trial. BMC Infect Dis. 2021;21(1): 1-8.
• [58] Mukhopadhyay K, Dalai CK, Singh R, Ahmed SN, Banerjee K. Do we have the Evidence to Repurpose Levamisole for Treatment of COVID 19?.CDTH. 2020;15. 1. https://doi.org/10.2174/1574885515999201231204530.
• [59] Fasa University of Medical Sciences. SiamackAfazeli. Evaluation of efficacy of levamisole and formoterol+budesonide in treatment of COVID-19. (2020). Available at: https://www.clinicaltrials.gov/ct2/show/NCT04331470. Accessed: 13th April, 2020.
• [60] Ain Shams University. FatmaSoliman E Ebeid. Levamisole and isoprinosine in immune-prophylaxis of Egyptian healthcare workers facing COVID-19. (2020) .Available at: https://clinicaltrials.gov/ct2/show/NCT04360122?term=levamisole&cond=COVID&draw=2&rank=2. Accessed: 5th May, 2020.
• [61] Cairo University. Mohamed El Dauroti. Levamisole and isoprinosine in the treatment of COVID19: A proposed therapeutic trial. (2020). Available at: https://clinicaltrials.gov/ct2/show/NCT04383717?term=levamisole&cond=COVID&draw=2&rank=3. Accessed: 13th May, 2020
• [62] WHO. COVID-19 vaccines. https://www.who.int/emergencies/diseases/novel-coronavirus-2019/covid-19-vaccines
• [63] WHO.WHO Coronavirus (COVID-19) Dashboard.https://covid19.who.int/
• [64] Worldometers . COVID-19 Coronavirus Pandemic. https://www.worldometers.info/coronavirus/