Safety of oral administration of high doses of ivermectin by means of biocompatible polyelectrolytes formulation
et al., Heliyon, doi:10.1016/j.heliyon.2020.e05820, Dec 2020
Ivermectin for COVID-19
4th treatment shown to reduce risk in
August 2020, now with p < 0.00000000001 from 106 studies, recognized in 24 countries.
No treatment is 100% effective. Protocols
combine treatments.
6,300+ studies for
210+ treatments. c19early.org
|
In vivo analysis of the safety of high dose ivermectin with a Corydoras fish animal model.
74 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 H7N771, Dengue37,72,73 , HIV-173, Simian virus 4074, Zika37,75,76 , West Nile76, Yellow Fever77,78, Japanese encephalitis77, Chikungunya78, Semliki Forest virus78, Human papillomavirus57, Epstein-Barr57, BK Polyomavirus79, and Sindbis virus78.
Ivermectin inhibits importin-α/β-dependent nuclear import of viral proteins71,73,74,80 , shows spike-ACE2 disruption at 1nM with microfluidic diffusional sizing38, binds to glycan sites on the SARS-CoV-2 spike protein preventing interaction with blood and epithelial cells and inhibiting hemagglutination41,81, shows dose-dependent inhibition of wildtype and omicron variants36, exhibits dose-dependent inhibition of lung injury61,66, may inhibit SARS-CoV-2 via IMPase inhibition37, may inhibit SARS-CoV-2 induced formation of fibrin clots resistant to degradation9, inhibits SARS-CoV-2 3CLpro54, may inhibit SARS-CoV-2 RdRp activity28, may minimize viral myocarditis by inhibiting NF-κB/p65-mediated inflammation in macrophages60, may be beneficial for COVID-19 ARDS by blocking GSDMD and NET formation82, may interfere with SARS-CoV-2's immune evasion via ORF8 binding4, may inhibit SARS-CoV-2 by disrupting CD147 interaction83-86, shows protection against inflammation, cytokine storm, and mortality in an LPS mouse model sharing key pathological features of severe COVID-1959,87, may be beneficial in severe COVID-19 by binding IGF1 to inhibit the promotion of inflammation, fibrosis, and cell proliferation that leads to lung damage8, may minimize SARS-CoV-2 induced cardiac damage40,48, may counter immune evasion by inhibiting NSP15-TBK1/KPNA1 interaction and restoring IRF3 activation88, may disrupt SARS-CoV-2 N and ORF6 protein nuclear transport and their suppression of host interferon responses1, reduces TAZ/YAP nuclear import, relieving SARS-CoV-2-driven suppression of IRF3 and NF-κB antiviral pathways35, increases Bifidobacteria which play a key role in the immune system89, has immunomodulatory51 and anti-inflammatory70,90 properties, and has an extensive and very positive safety profile91.
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Madrid et al., 31 Dec 2020, peer-reviewed, 8 authors.
Safety of oral administration of high doses of ivermectin by means of biocompatible polyelectrolytes formulation
Heliyon, doi:10.1016/j.heliyon.2020.e05820
The FDA-approved drug ivermectin is applied for treatments of onchocerciasis and lymphatic filariasis. The anticancer and anti-viral activities have been demonstrated stressing possibilities for the drug repurposing and therefore new information on high dosage safety is on demand. We analyzed in vivo tissue responses for high doses of ivermectin using Corydoras fish as animal model. We made intestinal histology and hematologic assays after oral administration of ivermectin transported with polyelectrolytes formulation. Histology showed any apparent damage of intestinal tissues at 0.22-170 mg of ivermectin/kg body weight. Immunofluorescence evidenced delocalization of Myosin-Vb at enterocytes only for the higher dose. Hematology parameters showed random variations after 7 days from administration, but a later apparent recover after 14 and 21 days. The study evaluated the potential of high doses of oral administration of ivermectin formulation, which could be an alternative with benefits in high compliance therapies.
Declaration of interests statement The authors declare no conflict of interest.
Additional information Supplementary content related to this article has been published online at https://doi.org/10.1016/j.heliyon.2020.e05820.
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