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Comparative study of the interaction of ivermectin with proteins of interest associated with SARS-CoV-2: A computational and biophysical approach

González-Paz et al., Biophysical Chemistry, doi:10.1016/j.bpc.2021.106677
Aug 2021  
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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.
4,500+ studies for 81 treatments. c19ivm.org
In Silico analysis of the components of ivermectin (avermectin-B1a and avermectin-B1b), suggesting different and complementary inhibitory activity of each component, with an affinity of avermectin-B1b for viral structures, and of avermectin-B1a for host structures.
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.
González-Paz et al., 19 Aug 2021, peer-reviewed, 9 authors.
In Silico studies are an important part of preclinical research, however results may be very different in vivo.
This PaperIvermectinAll
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