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Niclosamide for Covid-19: bridging the gap

Al-kuraishy et al., Molecular Biology Reports, doi:10.1007/s11033-021-06770-7
Oct 2021  
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Review of niclosamide as a potential treatment for COVID-19. Authors highlight the anti-inflammatory and antiviral effects of niclosamide, which modulates the release of pro-inflammatory cytokines, inhibits the NF-κB/NLRP3 inflammasome and mTOR signaling pathways, and interrupts the SARS-CoV-2 viral life-cycle. Niclosamide's low aqueous solubility is a limitation, but inhalational formulations and lipid nanoparticles are being explored to improve bioavailability and effectiveness against SARS-CoV-2. The review suggests niclosamide may reduce COVID-19 severity by attenuating acute lung injury and ARDS.
Reviews covering niclosamide for COVID-19 include1-6.
Al-kuraishy et al., 18 Oct 2021, peer-reviewed, 5 authors. Contact: alextha@yahoo.gr.
This PaperNiclosamideAll
Niclosamide for Covid-19: bridging the gap
Hayder M Al-Kuraishy, Ali I Al-Gareeb, Khalid J Alzahrani, Athanasios Alexiou, Gaber El-Saber Batiha
Molecular Biology Reports, doi:10.1007/s11033-021-06770-7
Aim/purpose Niclosamide (NCL) is an anthelminthic drug, which is widely used to treat various diseases due to its pleiotropic anti-inflammatory and antiviral activities. NCL modulates of uncoupling oxidative phosphorylation and different signaling pathways in human biological processes. The wide-spectrum antiviral effect of NCL makes it a possible candidate for recent pandemic SARS-CoV-2 infection and may reduce Covid-19 severity. Therefore, the aim of the present study was to review and clarify the potential role of NCL in Covid-19. Methods This study reviewed and highlighted the protective role of NCL therapy in Covid-19. A related literature search in PubMed, Scopus, Web of Science, Google Scholar, and Science Direct was done. Results NCL has noteworthy anti-inflammatory and antiviral effects. The primary antiviral mechanism of NCL is through neutralization of endosomal PH and inhibition of viral protein maturation. NCL acts as a proton carrier, inhibits homeostasis of endosomal PH, which limiting of viral proliferation and release. The anti-inflammatory effects of NCL are mediated by suppression of inflammatory signaling pathways and release of pro-inflammatory cytokines. However, the major limitation in using NCL is low aqueous solubility, which reduces oral bioavailability and therapeutic serum concentration that reducing the in vivo effect of NCL against SARS-CoV-2. Conclusions NCL has anti-inflammatory and immune regulatory effects by modulating the release of pro-inflammatory cytokines, inhibition of NF-κB /NLRP3 inflammasome and mTOR signaling pathway. NCL has an anti-SARS-CoV-2 effect via interruption of viral life-cycle and/or induction of cytopathic effect. Prospective clinical studies and clinical trials are mandatory to confirm the potential role of NCL in patients with Covid-19 concerning the severity and clinical outcomes.
Author contributions Manuscript preparation: HMAK, AIAG, KJA. Manuscript editing: GELSB, AA. Conflict of interest The authors declare that they have no competing interests. Publisher's Note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
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' 'Cell Res 27(8):1046–1064', 'journal-title': 'Cell Res'}, { 'key': '6770_CR67', 'doi-asserted-by': 'publisher', 'first-page': 'S28', 'DOI': '10.1016/j.tube.2019.04.008', 'volume': '116', 'author': 'X Fan', 'year': '2019', 'unstructured': 'Fan X, Xu J, Files M, Cirillo JD, Endsley JJ, Zhou J, Endsley MA (2019) ' 'Dual activity of niclosamide to suppress replication of integrated HIV-1 ' 'and Mycobacterium tuberculosis (Beijing). Tuberculosis 116:S28-33', 'journal-title': 'Tuberculosis'}, { 'key': '6770_CR68', 'doi-asserted-by': 'crossref', 'unstructured': 'Weiss A, Touret F, Baronti C, Gilles M, Hoen B, Nougairède A, de ' 'Lamballerie X, Sommer MO (2021) Niclosamide shows strong antiviral ' 'activity in a human airway model of SARS-CoV-2 infection and a conserved ' 'potency against the UK B. 1.1. 7 and SA B. 1.351 variant. bioRxiv', 'DOI': '10.1101/2021.04.26.441457'}, { 'issue': '1', 'key': '6770_CR69', 'doi-asserted-by': 'publisher', 'first-page': '145', 'DOI': '10.1080/14756366.2019.1690480', 'volume': '35', 'author': 'S Jo', 'year': '2020', 'unstructured': 'Jo S, Kim S, Shin DH, Kim MS (2020) Inhibition of SARS-CoV 3CL protease ' 'by flavonoids. J Enzyme Inhib Med Chem 35(1):145–151', 'journal-title': 'J Enzyme Inhib Med Chem'}, { 'key': '6770_CR70', 'doi-asserted-by': 'crossref', 'unstructured': 'Johnson TO, Adegboyega AE, Iwaloye O, Eseola OA, Plass W, Afolabi B, ' 'Rotimi D, Ahmed EI, Albrakati A, Batiha GE, Adeyemi OS (2021) ' 'Computational study of the therapeutic potentials of a new series of ' 'imidazole derivatives against SARS-CoV-2. J Pharmacol Sci', 'DOI': '10.1016/j.jphs.2021.05.004'}, { 'issue': '2', 'key': '6770_CR71', 'doi-asserted-by': 'publisher', 'first-page': '416', 'DOI': '10.1016/j.bbrc.2017.01.140', 'volume': '484', 'author': 'L Chen', 'year': '2017', 'unstructured': 'Chen L, Wang L, Shen H, Lin H, Li D (2017) Anthelminthic drug ' 'niclosamide sensitizes the responsiveness of cervical cancer cells to ' 'paclitaxel via oxidative stress-mediated mTOR inhibition. Biochem ' 'Biophys Res Commun 484(2):416–421', 'journal-title': 'Biochem Biophys Res Commun'}, { 'issue': '6', 'key': '6770_CR72', 'doi-asserted-by': 'publisher', 'first-page': 'e04050', 'DOI': '10.1016/j.heliyon.2020.e04050', 'volume': '6', 'author': 'N Niyomdecha', 'year': '2020', 'unstructured': 'Niyomdecha N, Suptawiwat O, Boonarkart C, Jitobaom K, Auewarakul P ' '(2020) Inhibition of human immunodeficiency virus type 1 by niclosamide ' 'through mTORC1 inhibition. Heliyon 6(6):e04050', 'journal-title': 'Heliyon'}, { 'issue': '5', 'key': '6770_CR73', 'doi-asserted-by': 'publisher', 'first-page': '319', 'DOI': '10.1038/s41577-021-00536-9', 'volume': '21', 'author': 'A Bonaventura', 'year': '2021', 'unstructured': 'Bonaventura A, Vecchié A, Dagna L, Martinod K, Dixon DL, Van Tassell BW, ' 'Dentali F, Montecucco F, Massberg S, Levi M, Abbate A (2021) Endothelial ' 'dysfunction and immunothrombosis as key pathogenic mechanisms in ' 'COVID-19. Nat Rev Immunol 21(5):319–329', 'journal-title': 'Nat Rev Immunol'}, { 'key': '6770_CR74', 'first-page': '1', 'volume': '27', 'author': 'S Engin', 'year': '2021', 'unstructured': 'Engin S, Yasar YK, Barut EN, Sezen SF (2021) Improved ' 'endothelium-dependent relaxation of thoracic aorta in ' 'niclosamide-treated diabetic rats. Cardiovasc Toxicol 27:1–9', 'journal-title': 'Cardiovasc Toxicol'}, { 'key': '6770_CR75', 'unstructured': 'Laubscher GJ, Lourens PJ, Venter C, Grobbelaar LM, Kell DB, Pretorius E ' '(2021) A decision-tree approach to treat platelet hyperactivity and ' 'anomalous blood clotting in acute COVID-19 patients. medRxiv'}, { 'key': '6770_CR76', 'first-page': '142', 'volume': '2', 'author': 'G Hamilton', 'year': '2017', 'unstructured': 'Hamilton G, Rath B (2017) Repurposing of anthelminthics as anticancer ' 'drugs. Oncomedicine 2:142–149', 'journal-title': 'Oncomedicine'}, { 'issue': '4', 'key': '6770_CR77', 'doi-asserted-by': 'publisher', 'first-page': '384', 'DOI': '10.1002/cbin.10915', 'volume': '42', 'author': 'R Ke', 'year': '2018', 'unstructured': 'Ke R, Xu Q, Li C, Luo L, Huang D (2018) Mechanisms of AMPK in the ' 'maintenance of ATP balance during energy metabolism. Cell Biol Int ' '42(4):384–392', 'journal-title': 'Cell Biol Int'}], 'container-title': 'Molecular Biology Reports', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://link.springer.com/content/pdf/10.1007/s11033-021-06770-7.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/article/10.1007/s11033-021-06770-7/fulltext.html', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://link.springer.com/content/pdf/10.1007/s11033-021-06770-7.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2023, 11, 11]], 'date-time': '2023-11-11T10:12:25Z', 'timestamp': 1699697545000}, 'score': 1, 'resource': {'primary': {'URL': 'https://link.springer.com/10.1007/s11033-021-06770-7'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2021, 10, 18]]}, 'references-count': 77, 'journal-issue': {'issue': '12', 'published-print': {'date-parts': [[2021, 12]]}}, 'alternative-id': ['6770'], 'URL': 'http://dx.doi.org/10.1007/s11033-021-06770-7', 'relation': {}, 'ISSN': ['0301-4851', '1573-4978'], 'subject': [], 'container-title-short': 'Mol Biol Rep', 'published': {'date-parts': [[2021, 10, 18]]}, 'assertion': [ { 'value': '10 June 2021', 'order': 1, 'name': 'received', 'label': 'Received', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '17 August 2021', 'order': 2, 'name': 'accepted', 'label': 'Accepted', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '18 October 2021', 'order': 3, 'name': 'first_online', 'label': 'First Online', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, {'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Declarations'}}, { 'value': 'The authors declare that they have no competing interests.', 'order': 2, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Conflict of interest'}}, { 'value': 'This content has been made available to all.', 'name': 'free', 'label': 'Free to read'}]}
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