Antiviral Activity of Repurposing Ivermectin against a Panel of 30 Clinical SARS-CoV-2 Strains Belonging to 14 Variants
et al., Pharmaceuticals, doi:10.3390/ph15040445, Apr 2022
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 vitro study with 30 COVID-19 strains from 14 variants, showing stronger efficacy with ivermectin compared to CQ and remdesivir, and relatively homogeneous efficacy with ivermectin regardless of strain/variant, in contrast to results for CQ and remdesivir.
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.
Study covers ivermectin, HCQ, and remdesivir.
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Delandre et al., 2 Apr 2022, peer-reviewed, 12 authors.
In vitro studies are an important part of preclinical research, however results may be very different in vivo.
Antiviral Activity of Repurposing Ivermectin against a Panel of 30 Clinical SARS-CoV-2 Strains Belonging to 14 Variants
Pharmaceuticals, doi:10.3390/ph15040445
Over the past two years, several variants of SARS-CoV-2 have emerged and spread all over the world. However, infectivity, clinical severity, re-infection, virulence, transmissibility, vaccine responses and escape, and epidemiological aspects have differed between SARS-CoV-2 variants. Currently, very few treatments are recommended against SARS-CoV-2. Identification of effective drugs among repurposing FDA-approved drugs is a rapid, efficient and low-cost strategy against SARS-CoV-2. One of those drugs is ivermectin. Ivermectin is an antihelminthic agent that previously showed in vitro effects against a SARS-CoV-2 isolate (Australia/VI01/2020 isolate) with an IC50 of around 2 µM. We evaluated the in vitro activity of ivermectin on Vero E6 cells infected with 30 clinically isolated SARS-CoV-2 strains belonging to 14 different variants, and particularly 17 strains belonging to six variants of concern (VOC) (variants related to Wuhan, alpha, beta, gamma, delta and omicron). The in vitro activity of ivermectin was compared to those of chloroquine and remdesivir. Unlike chloroquine (EC50 from 4.3 ± 2.5 to 29.3 ± 5.2 µM) or remdesivir (EC50 from 0.4 ± 0.3 to 25.2 ± 9.4 µM), ivermectin showed a relatively homogeneous in vitro activity against SARS-CoV-2 regardless of the strains or variants (EC50 from 5.1 ± 0.5 to 6.7 ± 0.4 µM), except for one omicron strain (EC50 = 1.3 ± 0.5 µM). Ivermectin (No. EC50 = 219, mean EC50 = 5.7 ± 1.0 µM) was, overall, more potent in vitro than chloroquine (No. EC50 = 214, mean EC50 = 16.1 ± 9.0 µM) (p = 1.3 × 10 −34 ) and remdesivir (No. EC50 = 201, mean EC50 = 11.9 ± 10.0 µM) (p = 1.6 × 10 −13 ). These results should be interpreted with caution regarding the potential use of ivermectin in SARS-CoV-2-infected patients: it is difficult to translate in vitro study results into actual clinical treatment in patients.
Supplementary Materials: The following supporting information can be downloaded at: www.mdpi.com/article/10.3390/ph15040445/s1, Table S1 : List of nucleotide and amino acid changes associated with the different SARS-CoV-2 variants.
Conflicts of Interest: The authors declare no conflicts of interest. The findings and conclusion of this report are those of the authors and do not represent the views of the Ministère des Armées and Ministère de l'Enseignement Supérieur, de la Recherche et de l'Innovation.
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