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The broad spectrum host-directed agent ivermectin as an antiviral for SARS-CoV-2 ?

Jans et al., Biochemical and Biophysical Research Communications, doi:10.1016/j.bbrc.2020.10.042
Jan 2021  
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Ivermectin for COVID-19
4th treatment shown to reduce risk in August 2020
 
*, now known with p < 0.00000000001 from 100 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.
3,800+ studies for 60+ treatments. c19ivm.org
Review of the potential of ivermectin as an antiviral against SARS-CoV-2 and COVID-19. Ivermectin targets the host nuclear transport protein importin alpha, which many RNA viruses hijack to enhance infection. Authors review evidence that ivermectin binds to and inhibits importin alpha, likely preventing nuclear import of viral proteins. In vitro studies indicate ivermectin has broad antiviral activity against HIV, dengue, Zika, West Nile, influenza, and SARS-CoV-2 at concentrations of 2-5 μM. Authors discuss ongoing clinical trials that will establish whether oral ivermectin is beneficial for COVID-19 treatment or prevention. Authors note that observational and retrospective studies report clinical improvements and reduced mortality with ivermectin, and that ivermectin may be a key therapeutic against COVID-19 and other viruses.
Jans et al., 31 Jan 2021, peer-reviewed, 2 authors. Contact: david.jans@monash.edu.
This PaperIvermectinAll
The broad spectrum host-directed agent ivermectin as an antiviral for SARS-CoV-2 ?
David A Jans, Kylie M Wagstaff
Biochemical and Biophysical Research Communications, doi:10.1016/j.bbrc.2020.10.042
a b s t r a c t FDA approved for parasitic indications, the small molecule ivermectin has been the focus of growing attention in the last 8 years due to its potential as an antiviral. We first identified ivermectin in a high throughput compound library screen as an agent potently able to inhibit recognition of the nuclear localizing Human Immunodeficiency Virus-1 (HIV-1) integrase protein by the host importin (IMP) a/b1 heterodimer, and recently demonstrated its ability to bind directly to IMPa to cause conformational changes that prevent its function in nuclear import of key viral as well as host proteins. Cell culture experiments have shown robust antiviral action towards a whole range of viruses, including HIV-1, dengue, Zika and West Nile Virus, Venezuelan equine encephalitis virus, Chikungunya, pseudorabies virus, adenovirus, and SARS-CoV-2 (COVID-19). Close to 70 clinical trials are currently in progress worldwide for SARS-CoV-2. Although few of these studies have been completed, the results that are available, as well as those from observational/retrospective studies, indicate clinical benefit. Here we discuss the case for ivermectin as a host-directed broad-spectrum antiviral agent, including for SARS-CoV-2.
Author contributions Conceptualization, D.A.J.; writingdoriginal draft preparation, D.A.J., K.M.W.; review and editing, D.A.J., K.M.W. Both authors have read and agreed to the published version of the manuscript. Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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