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All Studies   Meta Analysis    Recent:   

Remdesivir-ivermectin combination displays synergistic interaction with improved in vitro activity against SARS-CoV-2

Jeffreys et al., International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2022.106542 (date from preprint)
Dec 2020  
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Ivermectin for COVID-19
4th treatment shown to reduce risk in August 2020
 
*, now with p < 0.00000000001 from 104 studies, recognized in 23 countries.
No treatment is 100% effective. Protocols combine treatments. * >10% efficacy, ≥3 studies.
4,400+ studies for 79 treatments. c19ivm.org
In Vitro study showing enhanced antiviral activity of ivermectin and remdesivir in combination.
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.
Study covers ivermectin and remdesivir.
Jeffreys et al., 24 Dec 2020, peer-reviewed, 17 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperIvermectinAll
Remdesivir–ivermectin combination displays synergistic interaction with improved in vitro activity against SARS-CoV-2
Laura N Jeffreys, Shaun H Pennington, Jack Duggan, Claire H Caygill, Rose C Lopeman, Alastair F Breen, Jessica B Jinks, Alison Ardrey, Samantha Donnellan, Edward I Patterson, Grant L Hughes, David W Hong, Paul M O'neill, Ghaith Aljayyoussi, Andrew Owen, Stephen A Ward, Giancarlo A Biagini
International Journal of Antimicrobial Agents, doi:10.1016/j.ijantimicag.2022.106542
This is a PDF file of an article that has undergone enhancements after acceptance, such as the addition of a cover page and metadata, and formatting for readability, but it is not yet the definitive version of record. This version will undergo additional copyediting, typesetting and review before it is published in its final form, but we are providing this version to give early visibility of the article. Please note that, during the production process, errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.
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References
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Klotz, Ogbuokiri, Okonkwo, Ivermectin binds avidly to plasma proteins, Eur J Clin Pharmacol
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Odds, Synergy, antagonism, and what the chequerboard puts between them, J Antimicrob Chemother
Pizzorno, Padey, Dubois, Julien, Traversier et al., In vitro evaluation of antiviral activity of single and combined repurposable drugs against SARS-CoV-2, Antiviral Res
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Smit, Ochomo, Waterhouse, Kwambai, Abong et al., Pharmacokinetics-Pharmacodynamics of High-Dose Ivermectin with Dihydroartemisinin-Piperaquine on Mosquitocidal Activity and QT-Prolongation (IVERMAL), Clin Pharmacol Ther
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Who, WHO Coronovirus Disease (COVID-19) Dashboard
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