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 selective effect of Ivermectin on different human coronaviruses; in-vitro study

Shahin et al., Research Square, doi:10.21203/
Apr 2024  
  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 103 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.
4,100+ studies for 60+ treatments.
In Vitro study showing dose-dependent inhibition of wildtype and omicron SARS-CoV-2 with 0.5-5μM ivermectin.
Authors found no significant effect for alphacoronavirus NL63 and a moderate effect for betacoronavirus OC43. In contrast, ivermectin dramatically reduced SARS-CoV-2 wildtype and omicron viral particles by 90% and 95% respectively at 5μM, and showed inhibition starting at 0.5μM for omicron and 1μM for wildtype.
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), 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, shows dose-dependent inhibition of wildtype and omicron variants Shahin, 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, inhibits SARS-CoV-2 3CLpro Mody, may inhibit SARS-CoV-2 RdRp activity Parvez (B), may minimize viral myocarditis by inhibiting NF-κB/p65-mediated inflammation in macrophages Gao, 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.
Shahin et al., 18 Apr 2024, preprint, 7 authors.
In Vitro studies are an important part of preclinical research, however results may be very different in vivo.
This PaperIvermectinAll
The selective effect of Ivermectin on different human coronaviruses; in-vitro study
Amina Dakeh Shahin, Nofar Atari, Tal Meningher, Oran Erster, Dror Avni, Eli Schwartz, Michal Mandelboim
Background: The outbreak of coronavirus disease COVID-19, caused by Severe Acute Respiratory Coronavirus-2 (SARS-CoV-2) has become an urgent public health concern worldwide. Although several clinical trials have pointed to new drugs with some anti-COVID-19 activity, we are far from having a safe and effective drug. In this study, we tested the effect of ivermectin on several coronaviruses (serotypes), including variants of SARS-CoV-2. Methods: The effect of ivermectin was tested on cells infected with four different coronaviruses: NL63 (Alphacoronavirus genus.), OC43, SARS-CoV-2, and Omicron (all Betacoronavirus genus). Two hours post-infection, different doses of ivermectin were added to the cell culture. Results: There was no effect of even a high dose of ivermectin on NL63, however, we found a significant effect on OC43 PFU with a 40% inhibition at a dose of 5M. The impact of ivermectin on SARS-CoV-2 and on its Omicron variant was much more pronounced and at a dose of 5M there was inhibition of 90% and 95% respectively. Discussion: Although coronaviruses have been recognized as human pathogens for more than 50 years, no effective treatment strategy exists. Our current study did not demonstrate any effect of ivermectin on Alphacoronavirus but it had a specific impact on the Betacoronavirus genus with a mild impact on OC43 and a decidedly pronounced effect on SARS-CoV-2 including its Omicron variant. Ivermectin should be further studied as a single agent or as part of combined treatment against Coronaviruses.
Author Contributions: A.D.S., N. A., and T.M. performed the experiments. O. E. provided and calibrated the reagent for the RT-qPCR to all coronavirus variants. M. M., D. A., and E. S. conceived and planned the experiments, analyzed and interpreted the results supervised the project, and led the writing of the manuscript. All authors have read and agreed to the published version of the manuscript." Funding: Dakeh Shahin's fellowship was funded by The Meir and Edith Rosenfeld Foundation Institution Institutional Review Board Statement: All the experiments were done in cells in a culture with viruses that were also grown and isolated from cell culture. First isolation of Viruses were from positive nasopharyngeal swab samples. Since the virus was isolated from the swab media that was added to the cells in culture, and in practice no human tissue or material was used, according to the Institutional Review Board committee patient's consent was not required. This was approved by the Institutional Review Board, approval number 7875-20-SM Conflicts of Interest: The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results. Supplementary Files This is a list of supplementary les associated with this preprint. Click to download. supplementary.docx
Altschul, Gapped BLAST and PSI-BLAST: a new generation of protein database search programs, Nucleic Acids Res, doi:10.1093/nar/25.17.3389
Alvisi, Importin α/β-dependent nuclear transport of human parvovirus B19 nonstructural protein 1 is essential for viral replication, Antiviral research, doi:10.1016/j.antiviral.2023.105588
Bennett, Zhao, Bosard, Imperiale, Role of a nuclear localization signal on the minor capsid proteins VP2 and VP3 in BKPyV nuclear entry, Virology, doi:10.1016/j.virol.2014.10.013
Bernal, Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients, N Engl J Med, doi:10.1056/NEJMoa2116044
Biber, The effect of ivermectin on the viral load and culture viability in early treatment of nonhospitalized patients with mild COVID-19 -a double-blind, randomized placebo-controlled trial, International journal of infectious diseases : IJID : official publication of the International Society for Infectious Diseases, doi:10.1016/j.ijid.2022.07.003
Brucková, Mcintosh, Kapikian, Chanock, The Adaptation of Two Human Coronavirus Strains (OC38 and OC43) to Growth in Cell Monolayers, Proceedings of the Society for Experimental Biology and Medicine, doi:10.3181/00379727-135-35068
Bryant, Ivermectin for Prevention and Treatment of COVID-19 Infection: A Systematic Review, Meta-analysis, and Trial Sequential Analysis to Inform Clinical Guidelines, American journal of therapeutics, doi:10.1097/mjt.0000000000001402
Caly, Druce, Catton, Jans, Wagstaff, The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro, Antiviral research, doi:10.1016/j.antiviral.2020.104787
Chaouat, Anti-human ACE2 antibody neutralizes and inhibits virus production of SARS-CoV-2 variants of concern, iScience, doi:10.1016/j.isci.2022.104935
Cobos-Campos, Potential use of ivermectin for the treatment and prophylaxis of SARS-CoV-2 infection, Current research in translational medicine, doi:10.1016/j.retram.2021.103309
Corman, Detection of 2019 novel coronavirus (2019-nCoV) by real-time RT-PCR, Euro surveillance : bulletin Europeen sur les maladies transmissibles = European communicable disease bulletin, doi:10.2807/
Cui, Li, Shi, Origin and evolution of pathogenic coronaviruses, Nature reviews. Microbiology, doi:10.1038/s41579-018-0118-9
De La Rocha, Ivermectin compared with placebo in the clinical course in Mexican patients with asymptomatic and mild COVID-19: a randomized clinical trial, BMC infectious diseases, doi:10.1186/s12879-022-07890-6
Eweas, Alhossary, Abdel-Moneim, Molecular Docking Reveals Ivermectin and Remdesivir as Potential Repurposed Drugs Against SARS-CoV-2, Front Microbiol, doi:10.3389/fmicb.2020.592908
González Canga, The pharmacokinetics and interactions of ivermectin in humans--a mini-review, The AAPS journal, doi:10.1208/s12248-007-9000-9
Hajjar, Memish, Mcintosh, Middle East Respiratory Syndrome Coronavirus (MERS-CoV): a perpetual challenge, Annals of Saudi medicine, doi:10.5144/0256-4947.2013.427
Hammond, Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19, N Engl J Med, doi:10.1056/NEJMoa2118542
Herzog, Drosten, Müller, Plaque assay for human coronavirus NL63 using human colon carcinoma cells, Virology journal, doi:10.1186/1743-422x-5-138
Hill, Mirchandani, Pilkington, Ivermectin for COVID-19: Addressing Potential Bias and Medical Fraud, Open forum infectious diseases, doi:10.1093/ofid/ofab645ofab645
Jochmans, Leyssen, Neyts, A novel method for high-throughput screening to quantify antiviral activity against viruses that induce limited CPE, Journal of virological methods, doi:10.1016/j.jviromet.2012.04.011
Johnson, Loss of furin cleavage site attenuates SARS-CoV-2 pathogenesis, Nature, doi:10.1038/s41586-021-03237-4
Johnson-Arbor, Ivermectin: a mini-review, Clinical toxicology, doi:10.1080/15563650.2022.2043338
Kim, An, Kim, Hwang, Comparative efficacy and safety of pharmacological interventions for the treatment of COVID-19: A systematic review and network meta-analysis, PLoS medicine, doi:10.1371/journal.pmed.1003501
Kim, Antiviral effects of human placenta hydrolysate (Laennec(®)) against SARS-CoV-2 in vitro and in the ferret model, Journal of microbiology, doi:10.1007/s12275-021-1367-2
King, Tessier, Dodge, Weinberg, Mymryk, Inhibition of Human Adenovirus Replication by the Importin α/β1 Nuclear Import Inhibitor Ivermectin, Journal of virology, doi:10.1128/jvi.00710-20
Kow, Merchant, Mustafa, Hasan, The association between the use of ivermectin and mortality in patients with COVID-19: a meta-analysis, Pharmacological reports, doi:10.1007/s43440-021-00245-z
Laing, Gillan, Devaney, Ivermectin -Old Drug, New Tricks? Trends in parasitology, doi:10.1016/
Lehrer, Rheinsten, Ivermectin Docks to the SARS-CoV-2 Spike Receptor-binding Domain Attached to ACE2, Vivo, doi:10.21873/invivo.12134
Li, Ivermectin effectively inhibits hepatitis E virus replication, requiring the host nuclear transport protein importin α1, Archives of virology, doi:10.1007/s00705-021-05096-w
Lin, Identification of residues in the receptor-binding domain (RBD) of the spike protein of human coronavirus NL63 that are critical for the RBD-ACE2 receptor interaction, The Journal of general virology, doi:10.1099/vir.0.83331-0
Lustig, Neutralizing Response against Variants after SARS-CoV-2 Infection and One Dose of BNT162b2, N Engl J Med, doi:10.1056/NEJMc2104036
Malin, Suárez, Priesner, Fätkenheuer, Rybniker, Remdesivir against COVID-19 and Other Viral Diseases, Clinical microbiology reviews, doi:10.1128/cmr.00162-20
Mantlo, Bukreyeva, Maruyama, Paessler, Huang, Antiviral activities of type I interferons to SARS-CoV-2 infection, Antiviral research, doi:10.1016/j.antiviral.2020.104811
Martin, Jans, Antivirals that target the host IMPα/β1-virus interface, Biochem Soc Trans, doi:10.1042/bst20200568
Momekov, Momekova, Ivermectin as a potential COVID-19 treatment from the pharmacokinetic point of view: antiviral levels are not likely attainable with known dosing regimens, Biotechnology & Biotechnological Equipment, doi:10.1080/13102818.2020.1775118
Naeem, Antiviral potential of ivermectin against foot-and-mouth disease virus, serotype O, A and Asia-1, Microbial pathogenesis, doi:10.1016/j.micpath.2021.104914
Najjar-Debbiny, Effectiveness of Paxlovid in Reducing Severe COVID-19 and Mortality in High Risk Patients. Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, doi:10.1093/cid/ciac443
Patil, Verma, Masand, Prospective mode of action of Ivermectin: SARS-CoV-2, European journal of medicinal chemistry reports, doi:10.1016/j.ejmcr.2021.100018
Ravi, Saxena, Panda, Basic virology of SARS-CoV 2, Indian journal of medical microbiology, doi:10.1016/j.ijmmb.2022.02.005
Raza, Ivermectin Inhibits Bovine Herpesvirus 1 DNA Polymerase Nuclear Import and Interferes With Viral Replication, Microorganisms
Reis, Effect of Early Treatment with Ivermectin among Patients with Covid-19, N Engl J Med, doi:10.1056/NEJMoa2115869
Rozenberg, Evaluation of the relationship between quantitative PCR results and cell culturing of SARS2-CoV with respect to symptoms onset and Viral loada systematic review, medRxiv, doi:10.1101/2021.08.23.21262162
Saitou, Nei, The neighbor-joining method: a new method for reconstructing phylogenetic trees, Molecular Biology and Evolution, doi:10.1093/oxfordjournals.molbev.a040454
Santin, Scheim, Mccullough, Yagisawa, Borody, Ivermectin: a multifaceted drug of Nobel prizehonoured distinction with indicated efficacy against a new global scourge, COVID-19, New Microbes New Infect, doi:10.1016/j.nmni.2021.100924S2052-2975(21)00088-3
Schwartz, Does ivermectin have a place in the treatment of mild Covid-19?, New Microbes New Infect, doi:10.1016/j.nmni.2022.100985
Siedner, Ivermectin for the Treatment of COVID-19 Disease: Too Good to Pass Up or Too Good to Be True?, Open forum infectious diseases, doi:10.1093/ofid/ofab318
Siemieniuk, Drug treatments for covid-19: living systematic review and network meta-analysis, Bmj, doi:10.1136/bmj.m2980
Singh, Singh, Singh, Misra, Molnupiravir in COVID-19: A systematic review of literature, Diabetes & metabolic syndrome, doi:10.1016/j.dsx.2021.102329
Suputtamongkol, Ivermectin Accelerates Circulating Nonstructural Protein 1 (NS1) Clearance in Adult Dengue Patients: A Combined Phase 2/3 Randomized Double-blinded Placebo Controlled Trial, Clinical Infectious Diseases, doi:10.1093/cid/ciaa1332
Tamura, Nei, Kumar, Prospects for inferring very large phylogenies by using the neighbor-joining method, Proc Natl Acad Sci U S A, doi:10.1073/pnas.0404206101
Tamura, Stecher, Kumar, MEGA11: Molecular Evolutionary Genetics Analysis Version 11, Molecular Biology and Evolution, doi:10.1093/molbev/msab120
Wagstaff, Rawlinson, Hearps, Jans, An AlphaScreen®-based assay for high-throughput screening for specific inhibitors of nuclear import, Journal of biomolecular screening, doi:10.1177/1087057110390360
Wong, SARS, and Ebola: The Role of Super-Spreaders in Infectious Disease, Cell host & microbe, doi:10.1016/j.chom.2015.09.013
Wu, Li, Peng, Li, Crystal structure of NL63 respiratory coronavirus receptor-binding domain complexed with its human receptor, Proc Natl Acad Sci U S A, doi:10.1073/pnas.0908837106
Yesilbag, Toker, Ates, Ivermectin also inhibits the replication of bovine respiratory viruses (BRSV, BPIV-3, BoHV-1, BCoV and BVDV) in vitro, Virus research, doi:10.1016/j.virusres.2021.198384
Zaidi, Dehgani-Mobaraki, The mechanisms of action of ivermectin against SARS-CoV-2-an extensive review, The Journal of Antibiotics, doi:10.1038/s41429-021-00491-6
Zein, Sulistiyana, Raffaelo, Pranata, Ivermectin and mortality in patients with COVID-19: A systematic review, meta-analysis, and meta-regression of randomized controlled trials, Diabetes & metabolic syndrome, doi:10.1016/j.dsx.2021.102186
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