NICLOSAMIDE: A POTENTIAL TREATMENT OPTION FOR COVID-19
Keywords:SARS-CoV-2, COVID-19, Niclosamide, Oral formulation, repurposed drug, Oral bioavailability, Clinical trial
Coronavirus Disease 2019 (COVID-19) caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a global health hazard due to its rapid dissemination and limited treatment options. Identification of possible treatments that may kill the virus, speed up the recovery, or reduce the case fatality rate is a need of hour. However, developing and producing particular COVID-19 medicines and vaccines is a time-consuming process with possibilities of clinical failures due to safety or efficacy issue. Medication repositioning is a safer and quicker approach for dealing with the COVID-19 worldwide threat right now. Out of 48 FDA-approved medicines tested against the SARS-CoV-2, niclosamide is one amongst few that has shown potential in vitro antiviral activity against SARS-CoV-2. However, the currently available oral conventional formulation of niclosamide results in systemic medication levels those are unsatisfactory to inhibit SARS-CoV-2. Hence, various formulation strategies have been adapted in order to achieve optimum therapeutic outcome of niclosamide when delivered via oral, inhalation, and intranasal routes. Some of these formulations are presently undergoing clinical trials. The current review focuses on mechanisms of action of niclosamide and its repurposing effectiveness against COVID-19. The delivery strategies to improve its bioavailability have been overviewed. The recently completed and on-going clinical trials have also been summarized
Gil C, Ginex T, Maestro I, Nozal V, Barrado-Gil L, Cuesta-Geijo MÁ, Urquiza J, Ramírez D, Alonso C, Campillo NE, Martinez A. Covid-19: Drug Targets and Potential Treatments. J Med Chem. 2020 Nov 12;63(21):12359–86.
Biju P, K. P, Revadigar V, Dsouza S, Asif Iqbal M, Ahmed G. A review on the impact of the covid-19 pandemic on the health care sector. Int J Pharm Pharm Sci. 2021 Oct 1;1–6.
Petersen E, Koopmans M, Go U, Hamer DH, Petrosillo N, Castelli F, Storgaard M, Al Khalili S, Simonsen L. Comparing SARS-CoV-2 with SARS-CoV and influenza pandemics. Lancet Infect Dis. 2020 Sep;20(9):e238–44.
Singh TU, Parida S, Lingaraju MC, Kesavan M, Kumar D, Singh RK. Drug repurposing approach to fight COVID-19. Pharmacol Rep PR. 2020 Dec;72(6):1479–508.
Niharika D, Niharika B, Aishwarya T, Nikitha A, Butool R, Ibrahim M, Dharakesware R. Coronavirus-a virus in learning. Int J Curr Pharm Res. 2020 Jul 16;7–10.
Velavan TP, Meyer CG. The COVID-19 epidemic. Trop Med Int Health TM IH. 2020 Mar;25(3):278–80.
S P, Sundararajan M, A M. Insights into corona/coronavirus disease 2019 pandemic – opinion versus evidence. Asian J Pharm Clin Res. 2021 May 28;13–5.
Kifle ZD, Ayele AG, Enyew EF. Drug Repurposing Approach, Potential Drugs, and Novel Drug Targets for COVID-19 Treatment. J Environ Public Health. 2021;2021:6631721.
Russo A, Pellosi DS, Pagliara V, Milone MR, Pucci B, Caetano W, Hioka N, Budillon A, Ungaro F, Russo G, Quaglia F. Biotin-targeted Pluronic(®) P123/F127 mixed micelles delivering niclosamide: A repositioning strategy to treat drug-resistant lung cancer cells. Int J Pharm. 2016 Sep 10;511(1):127–39.
Jeon S, Ko M, Lee J, Choi I, Byun SY, Park S, Shum D, Kim S. Identification of Antiviral Drug Candidates against SARS-CoV-2 from FDA-Approved Drugs. Antimicrob Agents Chemother. 2020 Jun 23;64(7):e00819-20.
Xu J, Shi PY, Li H, Zhou J. Broad Spectrum Antiviral Agent Niclosamide and Its Therapeutic Potential. ACS Infect Dis. 2020 May 8;6(5):909–15.
Nagasree KP, Santhi K, Kumar RS, Jyothi BA, Lakshmi VJ. Review on drug repurposing. 2020;7(10):16.
Parmar MB, Panchal S. Drug reposition of non-cancer drugs for cancer treatments via pharmacovigilance approach - repurposing drugs in oncology. Asian J Pharm Clin Res. 2019 Jan 31;310–4.
Andrews P, Thyssen J, Lorke D. The biology and toxicology of molluscicides, Bayluscide. Pharmacol Ther. 1982;19(2):245–95.
Pearson RD, Hewlett EL. Niclosamide therapy for tapeworm infections. Ann Intern Med. 1985 Apr;102(4):550–1.
World Health Organization Model List of Essential Medicines.
Chen W, Mook RA, Premont RT, Wang J. Niclosamide: Beyond an antihelminthic drug. Cell Signal. 2018 Jan;41:89–96.
Kadri H, Lambourne OA, Mehellou Y. Niclosamide, a Drug with Many (Re)purposes. ChemMedChem. 2018 Jun 6;13(11):1088–91.
Ai N, Wood RD, Yang E, Welsh WJ. Niclosamide is a Negative Allosteric Modulator of Group I Metabotropic Glutamate Receptors: Implications for Neuropathic Pain. Pharm Res. 2016 Dec;33(12):3044–56.
Barbosa EJ, Löbenberg R, de Araujo GLB, Bou-Chacra NA. Niclosamide repositioning for treating cancer: Challenges and nano-based drug delivery opportunities. Eur J Pharm Biopharm Off J Arbeitsgemeinschaft Pharm Verfahrenstechnik EV. 2019 Aug;141:58–69.
Li SL, Yan J, Zhang YQ, Zhen CL, Liu MY, Jin J, Gao JL, Xiao XL, Shen X, Tai Y, Hu N, Zhang XZ, Sun ZJ, Dong DL. Niclosamide ethanolamine inhibits artery constriction. Pharmacol Res. 2017 Jan;115:78–86.
Liang L, Huang M, Xiao Y, Zen S, Lao M, Zou Y, Shi M, Yang X, Xu H. Inhibitory effects of niclosamide on inflammation and migration of fibroblast-like synoviocytes from patients with rheumatoid arthritis. Inflamm Res Off J Eur Histamine Res Soc Al. 2015 Apr;64(3–4):225–33.
Prather GR, MacLean JA, Shi M, Boadu DK, Paquet M, Hayashi K. Niclosamide As a Potential Nonsteroidal Therapy for Endometriosis That Preserves Reproductive Function in an Experimental Mouse Model. Biol Reprod. 2016 Oct 1;95(4):76.
Tao H, Zhang Y, Zeng X, Shulman GI, Jin S. Niclosamide ethanolamine-induced mild mitochondrial uncoupling improves diabetic symptoms in mice. Nat Med. 2014 Nov;20(11):1263–9.
Gwisai T, Hollingsworth NR, Cowles S, Tharmalingam N, Mylonakis E, Fuchs BB, Shukla A. Repurposing niclosamide as a versatile antimicrobial surface coating against device-associated, hospital-acquired bacterial infections. Biomed Mater Bristol Engl. 2017 Jul 12;12(4):045010.
Gassen NC, Niemeyer D, Muth D, Corman VM, Martinelli S, Gassen A, Hafner K, Papies J, Mösbauer K, Zellner A, Zannas AS, Herrmann A, Holsboer F, Brack-Werner R, Boshart M, Müller-Myhsok B, Drosten C, Müller MA, Rein T. SKP2 attenuates autophagy through Beclin1-ubiquitination and its inhibition reduces MERS-Coronavirus infection. Nat Commun. 2019 Dec 18;10(1):5770.
How to Cite
Copyright (c) 2022 SHWETA VIBHUTE, ADITI KASAR, HRISHIKESH MAHALE, MAHESH GAIKWAD, MADHUR KULKARNI
This work is licensed under a Creative Commons Attribution 4.0 International License.