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All Studies   Meta Analysis    Recent:   

Prophylactic administration of ivermectin attenuates SARS-CoV-2 induced disease in a Syrian Hamster Model

Uematsu et al., The Journal of Antibiotics, doi:10.1038/s41429-023-00623-0 (date from preprint)
Sep 2022  
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Ivermectin for COVID-19
4th treatment shown to reduce risk in August 2020
 
*, now with p < 0.00000000001 from 105 studies, recognized in 23 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,800+ studies for 95 treatments. c19ivm.org
Hamster study showing that prophylactic ivermectin inhibited COVID-19 weight loss, reduced lung viral titer by a factor of 10, inhibited pulmonary inflammatory cytokine expression, and reduced the severity of pathological changes with a single 1mg/kg dose. Authors also tested 250 and 500µg/kg for inhibition of weight loss, showing a dose-response relationship. While not statistically significant, 500µg/kg also showed a trend for benefit.
68 preclinical studies support the efficacy of ivermectin for COVID-19:
Ivermectin, better known for antiparasitic activity, is a broad spectrum antiviral with activity against many viruses including H7N766, Dengue32,67,68, HIV-168, Simian virus 4069, Zika32,70,71, West Nile71, Yellow Fever72,73, Japanese encephalitis72, Chikungunya73, Semliki Forest virus73, Human papillomavirus52, Epstein-Barr52, BK Polyomavirus74, and Sindbis virus73.
Ivermectin inhibits importin-α/β-dependent nuclear import of viral proteins66,68,69,75, shows spike-ACE2 disruption at 1nM with microfluidic diffusional sizing33, binds to glycan sites on the SARS-CoV-2 spike protein preventing interaction with blood and epithelial cells and inhibiting hemagglutination36,76, shows dose-dependent inhibition of wildtype and omicron variants31, exhibits dose-dependent inhibition of lung injury56,61, may inhibit SARS-CoV-2 via IMPase inhibition32, may inhibit SARS-CoV-2 induced formation of fibrin clots resistant to degradation5, inhibits SARS-CoV-2 3CLpro49, may inhibit SARS-CoV-2 RdRp activity24, may minimize viral myocarditis by inhibiting NF-κB/p65-mediated inflammation in macrophages55, may be beneficial for COVID-19 ARDS by blocking GSDMD and NET formation77, may inhibit SARS-CoV-2 by disrupting CD147 interaction78-81, shows protection against inflammation, cytokine storm, and mortality in an LPS mouse model sharing key pathological features of severe COVID-1954,82, may be beneficial in severe COVID-19 by binding IGF1 to inhibit the promotion of inflammation, fibrosis, and cell proliferation that leads to lung damage4, may minimize SARS-CoV-2 induced cardiac damage35,43, increases Bifidobacteria which play a key role in the immune system83, has immunomodulatory46 and anti-inflammatory65,84 properties, and has an extensive and very positive safety profile85.
Uematsu et al., 15 Sep 2022, peer-reviewed, 6 authors. Contact: tuematsu@insti.kitasato-u.ac.jp.
This PaperIvermectinAll
Prophylactic administration of ivermectin attenuates SARS-CoV-2 induced disease in a Syrian Hamster Model
Takayuki Uematsu, Tomomi Takano, Hidehito Matsui, Noritada Kobayashi, Satoshi Ōmura, Hideaki Hanaki
The Journal of Antibiotics, doi:10.1038/s41429-023-00623-0
, caused by SARS-CoV-2 infection, is currently among the most important public health concerns worldwide. Although several effective vaccines have been developed, there is an urgent clinical need for effective pharmaceutical treatments for treatment of COVID-19. Ivermectin, a chemical derivative of avermectin produced by Streptomyces avermitilis, is a macrocyclic lactone with antiparasitic activity. Recent studies have shown that ivermectin inhibits SARS-CoV-2 replication in vitro. In the present study, we investigated the in vivo effects of ivermectin in a hamster model of SARS-CoV-2 infection. The results of the present study demonstrate oral administration of ivermectin prior to SARS-CoV-2 infection in hamsters was associated with decreased weight loss and pulmonary inflammation. In addition, the administration of ivermectin reduced pulmonary viral titers and mRNA expression level of pro-inflammatory cytokines associated with severe COVID-19 disease. The administration of ivermectin rapidly induced the production of virus-specific neutralizing antibodies in the late stage of viral infection. Zinc concentrations leading to immune quiescence were also significantly higher in the lungs of ivermectin-treated hamsters compared to controls. These results indicate that ivermectin may have efficacy in reducing the development and severity of COVID-19 by affecting host immunity in a hamster model of SARS-CoV-2 infection.
Supplementary information The online version contains supplementary material available at https://doi.org/10.1038/s41429-023-00623-0. Infectious Diseases from the Japan Agency for Medical Research and Development, under grant JP20fk0108158 to HH. Compliance with ethical standards Conflict of interest The authors declare no competing interests. Publisher's note Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations. Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons. org/licenses/by/4.0/.
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The antiparasitic drug ivermectin is a novel FXR ligand ' 'that regulates metabolism. Nat Commun. 2013;4:1937.', 'journal-title': 'Nat Commun'}], 'container-title': 'The Journal of Antibiotics', 'original-title': [], 'language': 'en', 'link': [ { 'URL': 'https://www.nature.com/articles/s41429-023-00623-0.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://www.nature.com/articles/s41429-023-00623-0', 'content-type': 'text/html', 'content-version': 'vor', 'intended-application': 'text-mining'}, { 'URL': 'https://www.nature.com/articles/s41429-023-00623-0.pdf', 'content-type': 'application/pdf', 'content-version': 'vor', 'intended-application': 'similarity-checking'}], 'deposited': { 'date-parts': [[2023, 4, 25]], 'date-time': '2023-04-25T10:07:43Z', 'timestamp': 1682417263000}, 'score': 1, 'resource': {'primary': {'URL': 'https://www.nature.com/articles/s41429-023-00623-0'}}, 'subtitle': [], 'short-title': [], 'issued': {'date-parts': [[2023, 4, 25]]}, 'references-count': 40, 'alternative-id': ['623'], 'URL': 'http://dx.doi.org/10.1038/s41429-023-00623-0', 'relation': {}, 'ISSN': ['0021-8820', '1881-1469'], 'subject': ['Drug Discovery', 'Pharmacology'], 'container-title-short': 'J Antibiot', 'published': {'date-parts': [[2023, 4, 25]]}, 'assertion': [ { 'value': '5 January 2023', 'order': 1, 'name': 'received', 'label': 'Received', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '22 March 2023', 'order': 2, 'name': 'revised', 'label': 'Revised', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '5 April 2023', 'order': 3, 'name': 'accepted', 'label': 'Accepted', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'value': '25 April 2023', 'order': 4, 'name': 'first_online', 'label': 'First Online', 'group': {'name': 'ArticleHistory', 'label': 'Article History'}}, { 'order': 1, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Compliance with ethical standards'}}, { 'value': 'The authors declare no competing interests.', 'order': 2, 'name': 'Ethics', 'group': {'name': 'EthicsHeading', 'label': 'Conflict of interest'}}]}
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