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Ivermectin ameliorates acute myocarditis via the inhibition of importin-mediated nuclear translocation of NF-κB/p65

Gao et al., International Immunopharmacology, doi:10.1016/j.intimp.2024.112073
Apr 2024  
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Ivermectin for COVID-19
4th treatment shown to reduce risk in August 2020
 
*, now known with p < 0.00000000001 from 103 studies, recognized in 22 countries.
No treatment is 100% effective. Protocols combine complementary and synergistic treatments. * >10% efficacy in meta analysis with ≥3 clinical studies.
4,100+ studies for 60+ treatments. c19ivm.org
Mouse study showing that ivermectin improves cardiac function and reduces inflammation in models of viral and autoimmune myocarditis. Authors found that ivermectin inhibited the nuclear translocation of NF-κB/p65 in macrophages by targeting importin β, thereby reducing levels of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α. These effects were confirmed in both Coxsackie B3 virus (CVB3)-induced myocarditis and experimental autoimmune myocarditis (EAM) in BALB/c mice, as well as in CVB3-infected RAW264.7 macrophages treated with ivermectin or a selective NF-κB/p65 nuclear translocation inhibitor, cTN50. While not directly tested against SARS-CoV-2, these findings suggest that ivermectin's ability to suppress NF-κB/p65-mediated inflammation in macrophages may be beneficial in the context of COVID-19-associated myocarditis and cytokine storm.
Ivermectin, better known for antiparasitic activity, is a broad spectrum antiviral with activity against many viruses including H7N7 Götz, Dengue Jitobaom, Tay, Wagstaff, HIV-1 Wagstaff, Simian virus 40 Wagstaff (B), Zika Barrows, Jitobaom, Yang, West Nile Yang, Yellow Fever Mastrangelo, Varghese, Japanese encephalitis Mastrangelo, Chikungunya Varghese, Semliki Forest virus Varghese, Human papillomavirus Li, Epstein-Barr Li, BK Polyomavirus Bennett, and Sindbis virus Varghese.
Ivermectin inhibits importin-α/β-dependent nuclear import of viral proteins Götz, Kosyna, Wagstaff, Wagstaff (B), shows spike-ACE2 disruption at 1nM with microfluidic diffusional sizing Fauquet, binds to glycan sites on the SARS-CoV-2 spike protein preventing interaction with blood and epithelial cells and inhibiting hemagglutination Boschi, Scheim, shows dose-dependent inhibition of wildtype and omicron variants Shahin, exhibits dose-dependent inhibition of lung injury Abd-Elmawla, Ma, may inhibit SARS-CoV-2 via IMPase inhibition Jitobaom, may inhibit SARS-CoV-2 induced formation of fibrin clots resistant to degradation Vottero, inhibits SARS-CoV-2 3CLpro Mody, may inhibit SARS-CoV-2 RdRp activity Parvez (B), may minimize viral myocarditis by inhibiting NF-κB/p65-mediated inflammation in macrophages Gao, may be beneficial for COVID-19 ARDS by blocking GSDMD and NET formation Liu (C), shows protection against inflammation, cytokine storm, and mortality in an LPS mouse model sharing key pathological features of severe COVID-19 DiNicolantonio, Zhang, may be beneficial in severe COVID-19 by binding IGF1 to inhibit the promotion of inflammation, fibrosis, and cell proliferation that leads to lung damage Zhao, may minimize SARS-CoV-2 induced cardiac damage Liu, Liu (B), increases Bifidobacteria which play a key role in the immune system Hazan, has immunomodulatory Munson and anti-inflammatory DiNicolantonio (B), Yan properties, and has an extensive and very positive safety profile Descotes.
Gao et al., 17 Apr 2024, peer-reviewed, 6 authors.
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