Conv. Plasma
Nigella Sativa

All ivermectin studies
Meta analysis
study COVID-19 treatment researchIvermectinIvermectin (more..)
Melatonin Meta
Metformin Meta
Azvudine Meta
Bromhexine Meta Molnupiravir Meta
Budesonide Meta
Colchicine Meta
Conv. Plasma Meta Nigella Sativa Meta
Curcumin Meta Nitazoxanide Meta
Famotidine Meta Paxlovid Meta
Favipiravir Meta Quercetin Meta
Fluvoxamine Meta Remdesivir Meta
Hydroxychlor.. Meta Thermotherapy Meta
Ivermectin Meta

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  
  Source   PDF   All Studies   Meta AnalysisMeta
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.
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 @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
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
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.”
Ivermectin, better known for antiparasitic activity, is a broad spectrum antiviral with activity against many viruses including H7N7 Götz, Dengue Tay, Wagstaff, HIV-1 Wagstaff, Simian virus 40 Wagstaff (B), Zika Barrows, 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 induced formation of fibrin clots resistant to degradation Vottero, 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 Bifidobacterium which plays 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.
Buonfrate, Multiple-dose versus single-dose ivermectin for Strongyloides stercoralis infection (Strong Treat 1 to 4): a multicentre, open-label, phase 3, randomised controlled superiority trial, Lancet Infect. Dis
Caly, Wagstaff, Jans, Nuclear trafficking of proteins from RNA viruses: potential target for anti-virals?, Antivir. Res
Corman, Detection of 2019 novel coronavirus (2019-nCoV) by realtime RT-PCR, Euro Surveill
Dong, Hu, Gao, Discovering drugs to treat coronavirus disease 2019 (COVID-19), Drug Discov. Ther
Elfiky, Anti-HCV, nucleotide inhibitors, repurposing against COVID-19, Life Sci
Frieman, Severe acute respiratory syndrome coronavirus ORF6 antagonizes STAT1 function by sequestering nuclear import factors on the rough endoplasmic reticulum/Golgi membrane, J. Virol
Gonzalez Canga, The pharmacokinetics and interactions of ivermectin in humans-a mini-review, AAPS J
Gordon, The antiviral compound remdesivir potently inhibits RNA-dependent RNA polymerase from Middle East respiratory syndrome coronavirus, J. Biol. Chem
Gotz, Influenza A viruses escape from MxA restriction at the expense of efficient nuclear vRNP import, Sci. Rep
Hiscox, The coronavirus infectious bronchitis virus nucleoprotein localizes to the nucleolus, J. Virol
Jans, Martin, Wagstaff, Inhibitors of nuclear transport, Curr. Opin. Cell Biol
Ketkar, Lack of efficacy of ivermectin for prevention of a lethal Zika virus infection in a murine system, Diagn. Microbiol. Infect. Dis
Kosyna, The importin alpha/beta-specific inhibitor Ivermectin affects HIF-dependent hypoxia response pathways, Biol. Chem
Li, De Clercq, Therapeutic options for the 2019 novel coronavirus (2019-nCoV), Nat. Rev. Drug Discov
Lundberg, Nuclear import and export inhibitors alter capsid protein distribution in mammalian cells and reduce Venezuelan Equine Encephalitis Virus replication, Antivir. Res
Lv, Ivermectin inhibits DNA polymerase UL42 of pseudorabies virus entrance into the nucleus and proliferation of the virus in vitro and vivo, Antivir. Res
Mastrangelo, Ivermectin is a potent inhibitor of flavivirus replication specifically targeting NS3 helicase activity: new prospects for an old drug, J. Antimicrob. Chemother
Navarro, Safety of high-dose ivermectin: a systematic review and metaanalysis, J. Antimicrob. Chemother
Nicolas, Safety of oral ivermectin during pregnancy: a systematic review and meta-analysis, Lancet Global Health
Ono, Measles viruses on throat swabs from measles patients use signaling lymphocytic activation molecule (CDw150) but not CD46 as a cellular receptor, J. Virol
Rowland, Intracellular localization of the severe acute respiratory syndrome coronavirus nucleocapsid protein: absence of nucleolar accumulation during infection and after expression as a recombinant protein in vero cells, J. Virol
Tay, Nuclear localization of dengue virus (DENV) 1-4 non-structural protein 5; protection against all 4 DENV serotypes by the inhibitor Ivermectin, Antivir. Res
Timani, Nuclear/nucleolar localization properties of C-terminal nucleocapsid protein of SARS coronavirus, Virus Res
Van Der Watt, Targeting the nuclear import receptor Kpnbeta1 as an anticancer therapeutic, Mol. Canc. Therapeut
Wagstaff, An AlphaScreen(R)-based assay for high-throughput screening for specific inhibitors of nuclear import, J. Biomol. Screen
Wagstaff, Ivermectin is a specific inhibitor of importin alpha/betamediated nuclear import able to inhibit replication of HIV-1 and dengue virus, Biochem. J
Wang, Remdesivir and chloroquine effectively inhibit the recently emerged novel coronavirus (2019-nCoV) in vitro, Cell Res
Wulan, Nucleocytoplasmic transport of nucleocapsid proteins of enveloped RNA viruses, Front. Microbiol
Wurm, Localization to the nucleolus is a common feature of coronavirus nucleoproteins, and the protein may disrupt host cell division, J. Virol
Yamasmith, Efficacy and safety of ivermectin against dengue infection: a phase III, randomized, double-blind, placebo-controlled trial
Yang, The broad spectrum antiviral ivermectin targets the host nuclear transport importin alpha/beta1 heterodimer, Antivir. Res
Please send us corrections, updates, or comments. c19early involves the extraction of 100,000+ datapoints from thousands of papers. Community updates help ensure high accuracy. Vaccines and treatments are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment, vaccine, or intervention is 100% available and effective for all current and future variants. We do not provide medical advice. Before taking any medication, consult a qualified physician who can provide personalized advice and details of risks and benefits based on your medical history and situation. FLCCC and WCH provide treatment protocols.
  or use drag and drop