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All Studies   Meta Analysis    Recent:   

The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro

Caly et al., Antiviral Research, doi:10.1016/j.antiviral.2020.104787
Apr 2020  
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Ivermectin for COVID-19
4th treatment shown to reduce risk in August 2020
 
*, now known with p < 0.00000000001 from 101 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.
3,900+ studies for 60+ treatments. c19ivm.org
In Vitro study showing that ivermectin is an inhibitor of SARS-CoV-2, with a single addition to Vero-hSLAM cells 2h post infection with SARS-CoV-2 able to effect ~5000-fold reduction in viral RNA at 48h.
There are claims that this study shows that therapeutic concentrations cannot be reached in humans, however this is incorrect. The authors explain why using this in vitro study to determine the effective dose in vivo is a fallacy in this presentation web.archive.org @1:32. Authors indicate that the concentration required is very unlikely to be an issue. The study used monkey kidney cells (the only choice at the time of the experiments), which they note lack adaptive immune responses and do not produce interferon. Authors also note that ivermectin accumulates in lung and other tissues, and that the average lung concentration shown in modeling studies exceeds the effective level in their study. Authors have also repeated experiments with human lung cells showing 6-8 times improved IC50.
Tissue concentrations of ivermectin can be much higher than plasma concentration Lespine, Lifschitz.
Author's have also responded noting that "ivermectin's key direct target in mammalian cells is a not a viral component, but a host protein important in intracellular transport; the fact that it is a host-directed agent (HDA) is almost certainly the basis of its broad-spectrum activity against a number of different RNA viruses in vitro. The way a HDA can reduce viral load is by inhibiting a key cellular process that the virus hijacks to enhance infection by suppressing the host antiviral response. Reducing viral load by even a modest amount by using a HDA at low dose early in infection can be the key to enabling the body's immune system to begin to mount the full antiviral response before the infection takes control." Authors note that ivermectin works with the immune system and a 1:1 ratio of drug to virus is unlikely to be required web.archive.org.
In further research, authors note that they find efficacy for prophylactic use, and that smaller repeated doses is more efffective than a single larger dose web.archive.org.
Rajter et al. summarize the author, noting that “the antiviral activities of ivermectin have been derived from laboratory experiments that largely involve high, generally non physiologic, multiplicities of infection, and cell mono layer cultures, often of cell lines such as Vero cells that are not clinically relevant. The EC50 values should not be interpreted beyond the fact that they reveal robust, dose dependent antiviral activity in the cell model system used, and it would be naive to strive for μM concentrations of ivermectin in the clinic based on them.” sciencedirect.com.
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), inhibits SARS-CoV-2 3CLpro Mody, 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, 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, may inhibit SARS-CoV-2 RdRp activity Parvez (B), 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.
Caly et al., 3 Apr 2020, peer-reviewed, 5 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperIvermectinAll
The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro
Leon Caly, Julian D Druce, Mike G Catton, David A Jans, Kylie M Wagstaff
Antiviral Research, doi:10.1016/j.antiviral.2020.104787
Although several clinical trials are now underway to test possible therapies, the worldwide response to the COVID-19 outbreak has been largely limited to monitoring/containment. We report here that Ivermectin, an FDA-approved anti-parasitic previously shown to have broad-spectrum anti-viral activity in vitro, is an inhibitor of the causative virus (SARS-CoV-2), with a single addition to Vero-hSLAM cells 2 h post infection with SARS-CoV-2 able to effect ~5000-fold reduction in viral RNA at 48 h. Ivermectin therefore warrants further investigation for possible benefits in humans.
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