Nitazoxanide in the Treatment of COVID-19: A paradigm for Antiviral Drugs Targeting Host-Infected Cells

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Christian Brechot Jean-Francois Rossignol


Despite significant breakthroughs in the discovery of direct-acting antivirals for several viruses, there is a need for improvement. Thus, drugs able to target host-infected cells may prove valuable in enhancing the efficacy of antivirals and avoiding resistance due to viral genetic changes.

In this context, we summarize in this review the current knowledge on nitazoxanide's potential for treating COVID-19. Our review highlights nitazoxanide's very specific mode of action, targeting cellular energy through inhibiting mitochondrial oxidative phosphorylation (OXPHOS) and stimulating the innate immune response. Thus, nitazoxanide lowers the cellular ATP content and this leads to impaired viral replication and assembly. However, since nitazoxanide only yields a mild OXPHOS inhibition, this does not affect cell viability. Preclinical results and some clinical studies have suggested that nitazoxanide might be helpful for treating COVID-19. Indeed, some clinical studies have shown a decrease in severe COVID19 evolution as well as in viral multiplication; yet the results are still debated. Overall, the available information suggests the potential of nitazoxanide in association with direct-acting antivirals. In fact, this may hold true for other viruses than SARS-CoV-2 in the future. The impact of nitazoxanide on COVID-19 should be viewed as a paradigm for antiviral drugs targeting host-infected cells, and nitazoxanide should be part of the therapeutic tools for future emerging virus-related pandemics.

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BRECHOT, Christian; ROSSIGNOL, Jean-Francois. Nitazoxanide in the Treatment of COVID-19: A paradigm for Antiviral Drugs Targeting Host-Infected Cells. Medical Research Archives, [S.l.], v. 12, n. 4, apr. 2024. ISSN 2375-1924. Available at: <>. Date accessed: 27 may 2024. doi:
Review Articles


1. Keusch GT, Amuasi JH, Anderson DE, et al. Pandemic origins and a One Health approach to preparedness and prevention: Solutions based on SARS-CoV-2 and other RNA viruses. Proc Natl Acad Sci U S A. 2022;119(42):e2202871119. Doi:10.1073/pnas.2202871119
2. Netea MG, Ziogas A, Benn CS, et al. The role of trained immunity in COVID-19: Lessons for the next pandemic. Cell Host Microbe. 2023;31(6):890-901. Doi:10.1016/j.chom.2023.05.004
3. Rossignol J, Cavier R. Synthesis and antiparasitic activity of 2-benzamido nitrothiazoles. 1975:28216n.
4. Anderson VR, Curran MP. Nitazoxanide: a review of its use in the treatment of gastrointestinal infections. Drugs. 2007;67(13):1947-67. Doi:10.2165/00003495-200767130-00015
5. Rossignol JF. Nitazoxanide: a first-in-class broad-spectrum antiviral agent. Antiviral Res. Oct 2014;110:94-103. Doi:10.1016/j.antiviral.2014.07.014
6. Trabattoni D, Gnudi F, Ibba SV, et al. Thiazolides Elicit Anti-Viral Innate Immunity and Reduce HIV Replication. Sci Rep. Jun 2 2016;6:27148. Doi:10.1038/srep27148
7. Jasenosky LD, Cadena C, Mire CE, et al. The FDA-Approved Oral Drug Nitazoxanide Amplifies Host Antiviral Responses and Inhibits Ebola Virus. iScience. Sep 27 2019;19:1279-1290. Doi:10.1016/j.isci.2019.07.003
8. Ranjbar S, Haridas V, Nambu A, et al. Cytoplasmic RNA Sensor Pathways and Nitazoxanide Broadly Inhibit Intracellular Mycobacterium tuberculosis Growth. iScience. Dec 20 2019;22:299-313. Doi:10.1016/j.isci.2019.11.001
9. Senkowski W, Zhang X, Olofsson MH, et al. Three-Dimensional Cell Culture-Based Screening Identifies the Anthelmintic Drug Nitazoxanide as a Candidate for Treatment of Colorectal Cancer. Mol Cancer Ther. Jun 2015;14(6):1504-16. Doi:10.1158/1535-7163.MCT-14-0792
10. Hammad N, Ransy C, Pinson B, et al. Antiviral effect of thiazolides relies on mitochondrial mild uncoupling. bioRxiv. 2022:2022.09.16.508272. Doi:10.1101/2022.09.16.508272
11. Pouysségur J, Marchiq I, Parks SK, Durivault J, Ždralević M, Vucetic M. 'Warburg effect' controls tumor growth, bacterial, viral infections and immunity - Genetic deconstruction and therapeutic perspectives. Semin Cancer Biol. 2022;86(Pt 2):334-346. Doi:10.1016/j.semcancer.2022.07.004
12. Wang M, Cao R, Zhang L, et al. Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro. Cell Res. Mar 2020;30(3):269-271. Doi:10.1038/s41422-020-0282-0
13. Escalera A, Gonzalez-Reiche AS, Aslam S, et al. SARS-CoV-2 variants of concern have acquired mutations associated with an increased spike cleavage. bioRxiv. 2021:2021.08.05.455290. Doi:10.1101/2021.08.05.455290
14. Riccio A, Santopolo S, Rossi A, Piacentini S, Rossignol JF, Santoro MG. Impairment of SARS-CoV-2 spike glycoprotein maturation and fusion activity by nitazoxanide: an effect independent of spike variants emergence. Cell Mol Life Sci. Apr 7 2022;79(5):227. Doi:10.1007/s00018-022-04246-w
15. Miorin L, Mire CE, Ranjbar S, et al. The oral drug nitazoxanide restricts SARS-CoV-2 infection and attenuates disease pathogenesis in Syrian hamsters. bioRxiv. Feb 9 2022;Doi:10.1101/2022.02.08.479634
16. Piacentini S, Riccio A, Santopolo S, et al. The FDA-approved drug nitazoxanide is a potent inhibitor of human seasonal coronaviruses acting at postentry level: effect on the viral spike glycoprotein. bioRxiv. 2023:2022.07.13.499346. Doi:10.1101/2022.07.13.499346
17. Rossignol JF. Nitazoxanide, a new drug candidate for the treatment of Middle East respiratory syndrome coronavirus. J Infect Public Health. May-Jun 2016;9(3):227-30. Doi:10.1016/j.jiph.2016.04.001
18. Martins-Filho PR, do Nascimento-Junior EM, Barreto-Alves JA, Fakhouri R, Ferreira LC. Efficacy and safety of nitazoxanide in treating SARS-CoV-2 infection: a systematic review and meta-analysis of blinded, placebo-controlled, randomized clinical trials. Eur J Clin Pharmacol. Nov 2022;78(11):1813-1821. Doi:10.1007/s00228-022-03380-5
19. Mohamed Abuelazm, Ahmed Ghanem, Ahmed K. Awad, Ramadan Abdelmoez Farahat, Fatma Labieb, Basant E. Katamesh, Basel Abdelazeem. The Effect of Nitazoxanide on the Clinical Outcomes in Patients with COVID‑19: A Systematic Review and Meta‑Analysis of Randomized Controlled Trials Clinical Drug Investigation (2022) 42:1031–1047
20. Blum VF, Cimerman S, Hunter JR, et al. Nitazoxanide superiority to placebo to treat moderate COVID-19 - A Pilot prove of concept randomized double-blind clinical trial. EClinicalMedicine. Jul 2021;37:100981. Doi:10.1016/j.eclinm.2021.100981
21. Silva M, Espejo A, Pereyra ML, et al. Efficacy of Nitazoxanide in reducing the viral load in COVID-19 patients. Randomized, placebo-controlled, single-blinded, parallel group, pilot study. medRxiv. 2021:2021.03.03.21252509. Doi:10.1101/2021.03.03.21252509
22. Rocco PRM, Silva PL, Cruz FF, et al. Early use of nitazoxanide in mild COVID-19 disease: randomised, placebo-controlled trial. Eur Respir J. Jul 2021;58(1) Doi:10.1183/13993003.03725-2020
23. Rocco PRM, Silva PL, Cruz FF, et al. Nitazoxanide in Patients Hospitalized With COVID-19: A Multicentre, Randomized, Double-Blind, Placebo-Controlled Trial. Front Med (Lausanne). 2022;9:844728. Doi:10.3389/fmed.2022.844728
24. Rossignol JF, Bardin MC, Fulgencio J, Mogelnicki D, Brechot C. A randomized double-blind placebo-controlled clinical trial of nitazoxanide for treatment of mild or moderate COVID-19. EClinicalMedicine. Mar 2022;45:101310. Doi:10.1016/j.eclinm.2022.101310
25. Leventhal SS, Clancy C, Erasmus J, Feldmann H, Hawman DW. An Intramuscular DNA Vaccine for SARS-CoV-2 Decreases Viral Lung Load but Not Lung Pathology in Syrian Hamsters. Microorganisms. May 12 2021;9(5)Doi:10.3390/microorganisms9051040
26. Haffizulla J, Hartman A, Hoppers M, et al. Effect of nitazoxanide in adults and adolescents with acute uncomplicated influenza: a double-blind, randomised, placebo-controlled, phase 2b/3 trial. Lancet Infect Dis. Jul 2014;14(7):609-18. Doi:10.1016/S1473-3099(14)70717-0
27. Enriquez Lopez KY, Meneses Calderon J, de la Cruz Avila L, et al. Evolution of COVID-19 Pregnancies Treated with Nitazoxanide in a Third-Level Hospital. Cureus. May 13 2021;13(5):e15002. Doi:10.7759/cureus.15002
28. Stockis A, Deroubaix X, Lins R, Jeanbaptiste B, Calderon P, Rossignol JF. Pharmacokinetics of nitazoxanide after single oral dose administration in 6 healthy volunteers. Int J Clin Pharmacol Ther. Aug 1996;34(8):349-51.
29. Tan X, Hu L, Luquette LJ, 3rd, et al. Systematic identification of synergistic drug pairs targeting HIV. Nat Biotechnol. Nov 2012;30(11):1125-30. Doi:10.1038/nbt.2391