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:   

Ivermectin reduces in vivo coronavirus infection in a mouse experimental model

Arévalo et al., Scientific Reports, doi:10.1038/s41598-021-86679-0 (date from preprint)
Nov 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 102 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.
4,000+ studies for 60+ treatments.
Mouse study showing ivermectin reducing MHV viral load and disease. MHV is a type 2 family RNA coronavirus similar to SARS-CoV2.
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.
Arévalo et al., 2 Nov 2020, peer-reviewed, 12 authors.
This PaperIvermectinAll
Ivermectin reduces in vivo coronavirus infection in a mouse experimental model
A P Arévalo, R Pagotto, J L Pórfido, H Daghero, M Segovia, K Yamasaki, B Varela, M Hill, J M Verdes, M Duhalde Vega, M Bollati-Fogolín, M Crispo
Scientific Reports, doi:10.1038/s41598-021-86679-0
The objective of this study was to test the effectiveness of ivermectin for the treatment of mouse hepatitis virus (MHV), a type 2 family RNA coronavirus similar to SARS-CoV-2. Female BALB/cJ mice were infected with 6,000 PFU of MHV-A59 (group infected, n = 20) or infected and then immediately treated with a single dose of 500 µg/kg ivermectin (group infected + IVM, n = 20) or were not infected and treated with PBS (control group, n = 16). Five days after infection/treatment, the mice were euthanized and the tissues were sampled to assess their general health status and infection levels. Overall, the results demonstrated that viral infection induced typical MHV-caused disease, with the livers showing severe hepatocellular necrosis surrounded by a severe lymphoplasmacytic inflammatory infiltration associated with a high hepatic viral load (52,158 AU), while mice treated with ivermectin showed a better health status with a lower viral load (23,192 AU; p < 0.05), with only a few having histopathological liver damage (p < 0.05). No significant differences were found between the group infected + IVM and control group mice (P = NS). Furthermore, serum transaminase levels (aspartate aminotransferase and alanine aminotransferase) were significantly lower in the treated mice than in the infected animals. In conclusion, ivermectin diminished the MHV viral load and disease in the mice, being a useful model for further understanding this therapy against coronavirus diseases. Mouse hepatitis virus (MHV) is a single-stranded RNA coronavirus that targets different organs 1 . The virus is highly contagious, has natural respiratory or oral transmission, and shows high morbidity and low mortality rates. There is no vaccine or treatment available; therefore, upon infection, an entire laboratory mouse colony must be sacrificed to control the disease. Recent studies have shown that the mechanism of infection has similarities to that of SARS-CoV-2 2,3 : therefore, it has been proposed that MHV may be an interesting infection model to test new therapies against COVID-19 in animals. Although different therapies have been evaluated, no effective treatment is available, and the mechanism by which the virus enters the cell is being explored 4 . After entry into the cytoplasm of the host cell, coronaviruses rely on a nuclear transport system mediated by the importin α/β1 heterodimer to facilitate replication and infection 5, 6 . Some drugs have been demonstrated to act by impairing importin α/β1 heterodimer formation to prevent viral entry. Because both MHV and SARS-CoV-2 enter the nucleus via the same mechanism, MHV may be an interesting target for the development of candidate therapies against coronavirus infection in a mouse model. Ivermectin is an efficient and inexpensive drug usually applied to treat parasitic infestations. It has been approved by the FDA for animal and human use and is available worldwide. It has a wide margin of safety with an LD 50 of 30.. 15 min with an antibody mixture. The following fluorophore-conjugated antibodies were used: anti-CD4-FITC (#11,004,181, clone GK1.5) and anti-CD8-PE-Cy7 (#25,008,182, clone 53-6.7) from eBioscience (San Diego, CA, US) and anti-CD19-PerCP-Cy 5.5 (#551,001, clone ID3) from BD Pharmingen (San Diego, CA, US). Flow cytometry analysis was performed using an Attune Nxt Acoustic Focusing Cytometer (Thermo Fisher) equipped with a 488 nm laser. Emissions were detected using 530/30, 695/40 and 780/60 nm bandpass filters for FITC, PerCP-Cy5.5 and PE-Cy7, respectively. FlowJo software, version 10.6.1 (Tree Star, Ashland, Oregon, US), was used for data analysis. Unstained controls, single-color controls and fluorescence-minus-one controls were used to establish baseline gate settings for each respective antibody combination. Lymphocytes were gated based on their FSC and SSC dot plot profiles, and an FSC area vs FSC height dot plot was used to exclude doublets. B lymphocytes were defined as CD19-PerCP-Cy5.5-positive cells. For T lymphocyte analysis, a gate was placed on the CD19-negative population, and based on the PE-Cy7 vs FITC dot plot, CD8-PE-Cy7-positive cells and CD4-FITC-positive cells were defined as CD8 + and CD4 + lymphocytes, respectively. A minimum of 10,000 events in a single cell region were collected. The results are expressed as percentage of the specific cell type from the analyzed single-cell population. Statistical analysis...
Ashraf, Chaudhry, Raza, Ghosh, Zhao, In vitro activity of ivermectin against Staphylococcus aureus clinical isolates, Antimicrob. Resist. Infect. Control, doi:10.1186/s13756-018-0314-4
Barthold, Digestive System
Caly, Druce, Catton, Jans, Wagstaff, The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro, Antiviral Res, doi:10.1016/j.antiviral.2020.104787
Camp, Jonsson, A role for neutrophils in viral respiratory disease, Front. Immunol, doi:10.3389/fimmu.2017.00550
Carvalho, Verdelho Machado, New insights about albumin and liver disease, Ann. Hepatol, doi:10.5604/01.3001.0012.0916
Chaccour, The effect of early treatment with ivermectin on viral load, symptoms, doi:10.1016/j.eclinm.2020.100720
Chen, Subbarao, The Immunobiology of SARS*, Annu. Rev. Immunol, doi:10.1146/annurev.immunol.25.022106.141706
Ci, Avermectin exerts anti-inflammatory effect by downregulating the nuclear transcription factor kappa-B and mitogenactivated protein kinase activation pathway, Fundam. Clin. Pharmacol, doi:10.1111/j.1472-8206.2009.00684.x
Crump, Ivermectin: enigmatic multifaceted "wonder" drug continues to surprise and exceed expectations, J. Antibiot, doi:10.1038/ja.2017.11
Crump, Omura, Ivermectin, wonder drug" from Japan: The human use perspective, Proc. Jpn. Acad, doi:10.2183/pjab.87.13
Dias De Melo, Anti-COVID-19 efficacy of ivermectin in the golden hamster, doi:10.1101/2020.11.21.392639
Dominguez-Gomez, Ivermectin as an inhibitor of cancer stem-like cells, Mol. Med. Rep, doi:10.3892/mmr.2017.8231
Elea Phoenix, None
Fan, Cao, Kong, Zhang, Cryo-EM analysis of the post-fusion structure of the SARS-CoV spike glycoprotein, Nat. Commun, doi:10.1038/s41467-020-17371-6
Feng, Molecular pathology analyses of two fatal human infections of avian influenza A(H7N9) virus, J. Clin. Pathol, doi:10.1136/jclinpath-2014-202441
Gorial, Effectiveness of ivermectin as add-on therapy in COVID-19 management, doi:10.1101/2020.07.07.20145979
Guan, Clinical characteristics of coronavirus disease 2019 in China, N. Engl. J. Med, doi:10.1056/NEJMoa2002032
Heidary, Gharebaghi, Ivermectin: A systematic review from antiviral effects to COVID-19 complementary regimen, J. Antibiot, doi:10.1038/s41429-020-0336-z
Hu, Guo, Zhou, Shi, Characteristics of SARS-CoV-2 and COVID-19, Nat. Rev. Microbiol, doi:10.1038/s41579-020-00459-7
Jans, Wagstaff, Ivermectin as a broad-spectrum host-directed antiviral: The real deal?, Cells, doi:10.3390/cells9092100
Johansen, Animal and translational models of SARS-CoV-2 infection and COVID-19, Mucosal Immunol, doi:10.1038/s41385-020-00340-z
Korner, Majjouti, Alcazar, Mahabir, Of mice and men: The coronavirus MHV and mouse models as a translational approach to understand SARS-CoV-2, Viruses, doi:10.3390/v12080880
Kosyna, Nagel, Kluxen, Kraushaar, Depping, The importin alpha/beta-specific inhibitor Ivermectin affects HIF-dependent hypoxia response pathways, Biol. Chem, doi:10.1515/hsz-2015-0171
Krolewiecki, Antiviral effect of high-dose ivermectin in adults with COVID-19: A pilot randomised, controlled, open label multicentre trial, The Lancet, doi:10.2139/ssrn.3714649
Kyuwa, Acute hepatic failure in IFN-gamma-deficient BALB/c mice after murine coronavirus infection, Virus Res, doi:10.1016/s0168-1702(01)00432-4
Macphee, Dindzans, Fung, Levy, Acute and chronic changes in the microcirculation of the liver in inbred strains of mice following infection with mouse hepatitis virus type 3, Hepatology, doi:10.1002/hep.1840050422
Ochoa-Jaramillo, None
Perlman, Pathogenesis of coronavirus-induced infections. Review of pathological and immunological aspects, Adv. Exp. Med. Biol
Preusse, Schughart, Wilk, Klawonn, Pessler, Hematological parameters in the early phase of influenza A virus infection in differentially susceptible inbred mouse strains, BMC Res. Notes, doi:10.1186/s13104-015-1195-8
Procter, Clinical outcomes after early ambulatory multidrug therapy for high-risk SARS-CoV-2 (COVID-19) infection, Rev Cardiovasc Med, doi:10.31083/j.rcm.2020.04.260
Robinson, Harmon, O'farrelly, Liver immunology and its role in inflammation and homeostasis, Cell. Mol. Immunol, doi:10.1038/cmi.2016.3
Sajid, Iqbal, Muhammad, Iqbal, Immunomodulatory effect of various anti-parasitics: A review, Parasitology, doi:10.1017/s0031182005009108
Sharun, Ivermectin, a new candidate therapeutic against SARS-CoV-2/COVID-19, Ann. Clin. Microbiol. Antimicrob, doi:10.1186/s12941-020-00368-w
Smith, Walter, Walker, In Haschek and Rousseaux's Handbook of Toxicologic Pathology
Timani, Nuclear/nucleolar localization properties of C-terminal nucleocapsid protein of SARS coronavirus, Virus Res, doi:10.1016/j.virusres.2005.05.007
Vallejos, Ivermectin to prevent hospitalizations in patients with COVID-19 (IVERCOR-COVID19): A structured summary of a study protocol for a randomized controlled trial, Trials, doi:10.1186/s13063-020-04813-1
Wagstaff, Sivakumaran, Heaton, Harrich, Jans, Ivermectin is a specific inhibitor of importin α/βmediated nuclear import able to inhibit replication of HIV-1 and dengue virus, Biochem. J, doi:10.1042/BJ20120150
Weiss, Leibowitz, Coronavirus pathogenesis, Adv. Virus Res, doi:10.1016/B978-0-12-385885-6.00009-2
Wulan, Heydet, Walker, Gahan, Ghildyal, Nucleocytoplasmic transport of nucleocapsid proteins of enveloped RNA viruses, Front. Microbiol, doi:10.3389/fmicb.2015.00553
Zhang, Ivermectin inhibits LPS-induced production of inflammatory cytokines and improves LPS-induced survival in mice, Inflamm. Res, doi:10.1007/s00011-008-8007-8
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. Treatments and other interventions are complementary. All practical, effective, and safe means should be used based on risk/benefit analysis. No treatment 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