IVERMECTIN IN THE PREVENTION AND TREATMENT OF COVID-19
A Summary Statement
By Rob Rennebohm, MD
January 17, 2024
• History of IVM: In the late 1970s Dr. Omura, a Japanese microbiologist, discovered IVM.
Its first use was as an anti-parasitic drug, starting in 1987 (36 years ago). IVM has nearly
eliminated two terribly disfiguring and devastating diseases—river blindness and
elephantiasis. 36 years of safety studies have shown IVM to be a remarkably safe
medication. In 2015 Dr. Omura was awarded the Nobel Prize in Medicine for his
discovery of IVM.
• Treatment of COVID-19 with IVM has been far more extensively and carefully studied
than has treatment of COVID-19 with Paxlovid, Molnupiravir, or remdesivir.
o More than 95 clinical trials (78 of which have been published in peer-reviewed
journals)
o More than 2 dozen RCTs showing benefit from IVM
o Several Meta-analyses of RCTs showing benefit from IVM
o Many OCTs (observational controlled trials) showing benefit from IVM
o Many published reports of successful widespread government-sponsored IVM
distribution programs (in Peru, Argentina, Paraguay, Brazil, Mexico, Honduras,
India, and the Philippines, e.g.)
o In vitro studies: for example, Caly et al, have demonstrated that a single addition
of IVM to Vero-hSLAM cells 2 hours post infection with SARS-CoV-2 resulted in a
5000-fold reduction of viral RNA at 48 hours—i.e., completely eliminated the
virus by 48 hoars, suggesting that it is virus-cidal. (See more details about the
Caly study, including a diagram about its possible mechanism of action, at the
end of this article.)
o Since 2012 there have been at least a dozen published in vitro studies showing
that IVM is a broad spectrum antiviral agent. It has been shown to stop
replication of at least ten different viruses—e.g., influenza Zika, West Nile,
influenza, HIV, now SC-2—all RNA viruses.
• In contrast, Paxlovid and remdesivir were granted Emergency Use Authorization (EUA)
based on 1 RTC, each. The “rebound” phenomenon seen with Paxlovid suggests that it is
probably virus-static, rather than virus-cidal. And prophylactic use of Paxlovid has been
shown to be of no benefit (not to mention its impracticality and probably unsafe use as a
2
prophylactic agent for COVID-19). Whereas leaders of the prevailing COVID-19 narrative
have heavily promoted Paxlovid for routine use in treatment of COVID-19, they have
portrayed prescription of IVM as ridiculous and irresponsible use of a “horse dewormer.”
• Studies of the efficacy of IVM treatment of COVID-19 (RCTs, meta-analyses,
observational clinical trials, in vitro studies, animal studies, and analyses of widespread
IVM distribution programs) have suggested that that, overall, the efficacy of IVM is at
least comparable to the efficacy of alternative anti-viral therapies (Paxlovid,
Molnupiravir, and remdesivir) and is more effective (and far more practical) than
Paxlovid when used in the critically important prophylactic treatment of COVID-19.
Unfortunately, no RCTs have been conducted to compare IVM with Paxlovid (or
Molnupiravir or remdesivir) head-to-head. It is obvious that the leaders of the prevailing
COVID-19 narrative should have and could have carefully and honestly conducted such
head-to-head studies long ago, if they truly cared about treating COVID-19 in the best
possible way. It is also unfortunate that the pro-Paxlovid studies and the anti-IVM
studies that have been referenced by the promoters of the prevailing COVID-19 narrative
have been rife with conflict of interest and have been of questionable quality.
• The efficacy of the widespread IVM distribution campaign noted in Uttar Pradesh
deserves particular mention. Uttar Pradesh (UP) is a state in northern India with 231
million people. The Chief Minister of UP was a Hindu monk named Yogi Adityanath. In
mid-2020 UP started treating all close contacts of COVID patients and all health workers
with prophylactic IVM—as well as treating all COVID patients with early IVM treatment.
They noted impressive results. Prior to launching this initiative, their state had the 16th
lowest death rate in India. Three months later they had the 6th lowest death rate, and 2
months after that they were noticing almost no deaths.
By the summer of 2021 COVID appeared to be eradicated from UP. Cases had become
very rare. Only 0.004 % of tests for COVID were positive in UP. In contrast, in Kerala,
where IVM had been rejected, 19.7% of tests were positive for COVID at that same time.
WHO tried to attribute the UP success to vaccination and did not mention UP’s use of
IVM. But only 10% of UP citizens were fully vaccinated.
Other states in India had started using prophylactic HCQ for health care workers, starting
in March 2020. The Indian Council of Medical Research promptly conducted a trial and
found that prophylactic HCQ reduced infection rates by up to 80% in these health care
workers. This prompted an eventual visit to India by Bill Gates in September 2021.
Perhaps, India was having too much success with HCQ and IVM? Two days after his visit
both IVM and HCQ were dropped from India’s national guidelines.
3
Similar IVM distribution programs in Mexico, Argentina, Brazil, Paraguay, Peru, and the
Philippines have also appeared to show impressive success.
• The experience of widespread IVM distribution campaigns in Peru also warrants special
mention. From April 1, 2020, until October 31, 2020, a mass IVM distribution program
was initiated in 8 Peruvian states—but not in the highly populated city of Lima, whose
city government rejected use of IVM. Peru’s IVM distribution program was associated
with a massive reduction in cases and deaths. The case fatality rate (CFR) plummeted in
the 8 states that implemented use of IVM. The CFR in Lima was far worse.
Specifically, excess deaths fell by a mean of 74% in the states that implemented a
widespread IVM distribution program. Excess deaths decreased 14-fold during the IVM
distribution program and then increased 13-fold after IVM distribution programs were
discontinued when a new (anti-IVM) President took office in Peru.
• The safety of IVM has been established to a far greater extent (36 years of experience)
than has the safety of Paxlovid, Molnupiravir, or remdesivir. IVM is extremely safe. In
comparison, Paxlovid, Molnupiravir, and remdesivir are very new and far less safe.
• IVM is inexpensive. Paxlovid, Molnupiravir, and remdesivir are very expensive.
• The leaders of the prevailing COVID-19 narrative have deliberately, unscientifically,
unethically, and wrongly demonized and ignored IVM, and, appallingly, have punished
and even delicensed physicians who have sought to help patients by prescribing IVM.
• It is high time for physicians to stop being hesitant, defensive, and afraid to even
mention IVM as a treatment option (out of fear of being ridiculed or punished by their
colleagues, administrators, or friends). It is time for physicians to confidently state that
IVM is our best, most scientifically-sound anti-viral option for COVID-19— when safety,
cost, practicality, availability, the extent of scientific study, quality of studies, honesty,
and extent of conflict of interest are taken into account. It is the physicians who have
been prescribing Paxlovid (and certainly remdesivir and Molnupiravir) who should be
feeling hesitant and defensive about promoting use of Paxlovid, Molnupiravir, and
remdesivir and embarrassed to have belittled, demonized and ignored IVM. Physicians
who have refused to prescribe IVM and pharmacists who have refused to fill such
prescriptions should think about the effects of that behavior on patient care—not only
on an individual patient level, but also on a population level and a global level.
• At the same time we must realize that all of the available anti-viral therapies, including
IVM, are of limited value. The relative risk reduction reported in studies with all of
these anti-viral therapies, including IVM, has often been quite modest.
• It is noteworthy, however, that Dr. Omura, who was awarded the Nobel Prize for his
discovery of IVM, strongly endorses the use and further study of IVM for COVID-19. In
4
fact, the people who have been most enthusiastic about the use of IVM for prophylaxis
and early treatment of COVID-19 have been the physicians who have actually treated
large numbers of COVID patients with IVM. There is still a place for clinical judgment in
medicine. Thoughtful analysis of clinical experience needs to be honored.
FURTHER DETAILS ABOUT THE IN VITRO STUDY BY CALY ET AL:
Leon Caly, Julian D. Druce, Mike G. Catton, David A. Jans, Kylie M. Wagstaff.
The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro.
Antiviral Research, Volume 178, 2020, 104787, ISSN 0166-3542,
https://doi.org/10.1016/j.antiviral.2020.104787.
(https://www.sciencedirect.com/science/article/pii/S0166354220302011)
Abstract: 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-CoV2 able to effect ~5000-fold reduction in viral RNA at 48 h. Ivermectin therefore warrants
further investigation for possible benefits in humans.
A single addition of IVM to Vero-hSLAM cells 2 hours post infection with SARS-CoV-2 resulted in
a 5000 fold reduction of viral RNA at 48 hours—i.e., completely eliminated the virus by 48 hrs.
The authors propose that IVM to inhibits integrase protein (IN) and the Importin alpha/beta 1
heterodimer responsible for IN nuclear import.
As depicted in the drawing below, IMPα/β1 binds to the coronavirus cargo protein in the
cytoplasm (top) and translocates it through the nuclear pore complex (NPC) into the nucleus
where the complex falls apart and the viral cargo can reduce the host cell’s antiviral response,
leading to enhanced infection. Ivermectin binds to and destabilizes the
Impα/β1 heterodimer thereby preventing Impα/β1 from binding to the viral protein (bottom)
and preventing it from entering the nucleus. This likely results in reduced inhibition of the
antiviral responses, leading to a normal, more efficient antiviral response.
5
The authors hypothesize that the beneficial effect of IVM is likely through inhibiting IMPα/β1-
mediated nuclear import of viral proteins, as has been shown for other RNA viruses. This
probably represents only one of several possible mechanisms by which IVM inhibits SARSCoV-2.
FURTHER READING:
Please see the extensive discussion of IVM on the FLCCC website:

Treatment Protocols

Also, see:
Pierre Kory’s important book, The War on Ivermectin.
FURTHER REFERENCES:
1. Abd-Elmawla et al., Suppression of NLRP3 inflammasome by ivermectin ameliorates
bleomycin-induced pulmonary fibrosis, Journal of Zhejiang University-SCIENCE
B, springer.com, doi.org.
2. Albariqi et al., Pharmacokinetics and Safety of Inhaled Ivermectin in Mice as a Potential
COVID-19 Treatment, International Journal of Pharmaceutics, sciencedirect.com, doi.org.
6
3. Alvarado et al., Interaction of the New Inhibitor Paxlovid (PF-07321332) and Ivermectin With
the Monomer of the Main Protease SARS-CoV-2: A Volumetric Study Based on Molecular
Dynamics, Elastic Networks, Classical Thermodynamics and SPT, Computational Biology and
Chemistry, sciencedirect.com, doi.org.
4. Aminpour et al., In Silico Analysis of the Multi-Targeted Mode of Action of Ivermectin and
Related Compounds, Computation, mdpi.com, doi.org.
5. Arévalo et al., Ivermectin reduces in vivo coronavirus infection in a mouse experimental
model, Scientific Reports, nature.com, doi.org.
6. Barrows et al., A Screen of FDA-Approved Drugs for Inhibitors of Zika Virus Infection, Cell
Host & Microbe, sciencedirect.com, doi.org.
7. Bello et al., Elucidation of the inhibitory activity of ivermectin with host nuclear importin α
and several SARS-CoV-2 targets, Journal of Biomolecular Structure and
Dynamics, tandfonline.com, doi.org.
8. Bennett et al., Role of a nuclear localization signal on the minor capsid Proteins VP2 and VP3
in BKPyV nuclear entry, Virology, sciencedirect.com, doi.org.
9. Boschi et al., SARS-CoV-2 Spike Protein Induces Hemagglutination: Implications for COVID-19
Morbidities and Therapeutics and for Vaccine Adverse Effects, bioRxiv, biorxiv.org, doi.org.
10. Caly et al., The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in
vitro, Antiviral Research, sciencedirect.com, doi.org.
11. Chaccour et al., Nebulized ivermectin for COVID-19 and other respiratory diseases, a proof
of concept, dose-ranging study in rats, Scientific Reports, nature.com, doi.org.
12. Chellasamy et al., Docking and molecular dynamics studies of human ezrin protein with a
modelled SARS-CoV-2 endodomain and their interaction with potential invasion inhibitors,
Journal of King Saud University – Science, sciencedirect.com, doi.org.
13. Choudhury et al., Exploring the binding efficacy of ivermectin against the key proteins of
SARS-CoV-2 pathogenesis: an in silico approach, Future Medicine, futuremedicine.com, doi.org.
14. Croci et al., Liposomal Systems as Nanocarriers for the Antiviral Agent Ivermectin,
International Journal of Biomaterials, hindawi.com, doi.org.
15. De Forni et al., Synergistic drug combinations designed to fully suppress SARS-CoV-2 in the
lung of COVID-19 patients, PLoS ONE, plos.org, doi.org.
16. de Melo et al., Attenuation of clinical and immunological outcomes during SARS-CoV-2
infection by ivermectin, EMBO Mol. Med., embopress.org, doi.org.
17. Delandre et al., Antiviral Activity of Repurposing Ivermectin against a Panel of 30 Clinical
SARS-CoV-2 Strains Belonging to 14 Variants, Pharmaceuticals, mdpi.com, doi.org.
18. Descotes, J., Medical Safety of Ivermectin, ImmunoSafe Consultance, medincell.com.
7
19. DiNicolantonio et al., Ivermectin may be a clinically useful anti-inflammatory agent for latestage COVID-19, Open Heart, bmj.com, doi.org.
20. DiNicolantonio (B) et al., Anti-inflammatory activity of ivermectin in late-stage COVID-19
may reflect activation of systemic glycine receptors, Open Heart, bmj.com, doi.org.
21. Errecalde et al., Safety and Pharmacokinetic Assessments of a Novel Ivermectin Nasal Spray
Formulation in a Pig Model, Journal of Pharmaceutical Sciences, sciencedirect.com, doi.org.
22. Eweas et al., Molecular Docking Reveals Ivermectin and Remdesivir as Potential Repurposed
Drugs Against SARS-CoV-2, Frontiers in Microbiology, frontiersin.org, doi.org.
23. Fauquet et al., Microfluidic Diffusion Sizing Applied to the Study of Natural Products and
Extracts That Modulate the SARS-CoV-2 Spike RBD/ACE2 Interaction,
Molecules, mdpi.com, doi.org.
24. Francés-Monerris et al., Microscopic interactions between ivermectin and key human and
viral proteins involved in SARS-CoV-2 infection, Physical Chemistry Chemical
Physics, rsc.org, doi.org.
25. Francés-Monerris (B) et al., Has Ivermectin Virus-Directed Effects against SARS-CoV-2?
Rationalizing the Action of a Potential Multitarget Antiviral Agent,
ChemRxiv, chemrxiv.org, doi.org.
26. García-Aguilar et al., In Vitro Analysis of SARS-CoV-2 Spike Protein and Ivermectin
Interaction, International Journal of Molecular Sciences, mdpi.com, doi.org.
27. González-Paz et al., Comparative study of the interaction of ivermectin with proteins of
interest associated with SARS-CoV-2: A computational and biophysical approach, Biophysical
Chemistry, sciencedirect.com, doi.org.
28. González-Paz (B) et al., Structural Deformability Induced in Proteins of Potential Interest
Associated with COVID-19 by binding of Homologues present in Ivermectin: Comparative Study
Based in Elastic Networks Models, Journal of Molecular Liquids, sciencedirect.com, doi.org.
29. Götz et al., Influenza A viruses escape from MxA restriction at the expense of efficient
nuclear vRNP import, Scientific Reports, nature.com, doi.org.
30. Hazan et al., Treatment with Ivermectin Increases the Population of Bifidobacterium in the
Gut, ACG 2023, eventscribe.net.
31. Jeffreys et al., Remdesivir-ivermectin combination displays synergistic interaction with
improved in vitro activity against SARS-CoV-2, International Journal of Antimicrobial
Agents, sciencedirect.com, doi.org.
32. Jitobaom et al., Synergistic anti-SARS-CoV-2 activity of repurposed anti-parasitic drug
combinations, BMC Pharmacology and Toxicology, biomedcentral.com, doi.org.
33. Jitobaom (B) et al., Favipiravir and Ivermectin Showed in Vitro Synergistic Antiviral Activity
against SARS-CoV-2, Research Square, researchsquare.com, doi.org.
8
34. Kern et al., Modeling of SARS-CoV-2 Treatment Effects for Informed Drug Repurposing,
Frontiers in Pharmacology, frontiersin.org, doi.org.
35. Kosyna et al., The importin α/β-specific inhibitor Ivermectin affects HIF-dependent hypoxia
response pathways, Biological Chemistry, degruyter.com, doi.org.
36. Lehrer et al., Ivermectin Docks to the SARS-CoV-2 Spike Receptor-binding Domain Attached
to ACE2, In Vivo, 34:5, 3023-3026, iiarjournals.org, doi.org.
37. Li et al., Quantitative proteomics reveals a broad-spectrum antiviral property of ivermectin,
benefiting for COVID-19 treatment, J. Cellular Physiology, wiley.com, doi.org.
38. Liu et al., SARS-CoV-2 viral genes Nsp6, Nsp8, and M compromise cellular ATP levels to
impair survival and function of human pluripotent stem cell-derived cardiomyocytes, Stem Cell
Research & Therapy, biomedcentral.com, doi.org.
39. Liu (B) et al., Genome-wide analyses reveal the detrimental impacts of SARS-CoV-2 viral
gene Orf9c on human pluripotent stem cell-derived cardiomyocytes, Stem Cell
Reports, sciencedirect.com, doi.org.
40. Liu (C) et al., Crosstalk between neutrophil extracellular traps and immune regulation:
insights into pathobiology and therapeutic implications of transfusion-related acute lung injury,
Frontiers in Immunology, frontiersin.org, doi.org.
41. Ma et al., Ivermectin contributes to attenuating the severity of acute lung injury in mice,
Biomedicine & Pharmacotherapy, sciencedirect.com, doi.org.
42. Madrid et al., Safety of oral administration of high doses of ivermectin by means of
biocompatible polyelectrolytes formulation, Heliyon, sciencedirect.com, doi.org.
43. Mastrangelo et al., Ivermectin is a potent inhibitor of flavivirus replication specifically
targeting NS3 helicase activity: new prospects for an old drug, Journal of Antimicrobial
Chemotherapy, oup.com, doi.org.
44. Mody et al., Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential
anti-SARS-CoV-2 agents, Communications Biology, nature.com, doi.org.
45. Mountain Valley MD, Mountain Valley MD Receives Successful Results From BSL-4 COVID19 Clearance Trial on Three Variants Tested With Ivectosol™, globenewswire.com.
46. Munson et al., Niclosamide and ivermectin modulate caspase-1 activity and
proinflammatory cytokine secretion in a monocytic cell line, British Society For Nanomedicine
Early Career Researcher Summer Meeting, 2021, archive.org.
47. Muthusamy et al., Virtual Screening Reveals Potential Anti-Parasitic Drugs Inhibiting the
Receptor Binding Domain of SARS-CoV-2 Spike protein, Journal of Virology & Antiviral
Research, scitechnol.com.
9
48. Parvez et al., Insights from a computational analysis of the SARS-CoV-2 Omicron variant:
Host–pathogen interaction, pathogenicity, and possible drug therapeutics, Immunity,
Inflammation and Disease, wiley.com, doi.org.
49. Qureshi et al., Mechanistic insights into the inhibitory activity of FDA approved ivermectin
against SARS-CoV-2: old drug with new implications, Journal of Biomolecular Structure and
Dynamics, tandfonline.com, doi.org.
50. Rana et al., A Computational Study of Ivermectin and Doxycycline Combination Drug
Against SARS-CoV-2 Infection, Research Square, researchsquare.com, doi.org.
51. Saha et al., The Binding mechanism of ivermectin and levosalbutamol with spike protein of
SARS-CoV-2, Structural Chemistry, researchsquare.com, doi.org.
52. Saha (B) et al., Manipulation of Spray-Drying Conditions to Develop an Inhalable Ivermectin
Dry Powder, Pharmaceutics, mdpi.com, doi.org.
53. Scheim et al., Sialylated Glycan Bindings from SARS-CoV-2 Spike Protein to Blood and
Endothelial Cells Govern the Severe Morbidities of COVID-19, International Journal of Molecular
Sciences, mdpi.com, doi.org.
54. Schöning et al., Highly-transmissible Variants of SARS-CoV-2 May Be More Susceptible to
Drug Therapy Than Wild Type Strains, Research Square, researchsquare.com, doi.org.
55. Segatori et al., Effect of Ivermectin and Atorvastatin on Nuclear Localization of Importin
Alpha and Drug Target Expression Profiling in Host Cells from Nasopharyngeal Swabs of SARSCoV-2- Positive Patients, Viruses, mdpi.com, doi.org.
56. Suravajhala et al., Comparative Docking Studies on Curcumin with COVID-19 Proteins, MDPI
AG, preprints.org, doi.org.
57. Surnar et al., Clinically Approved Antiviral Drug in an Orally Administrable Nanoparticle for
COVID-19, ACS Pharmacol. Transl. Sci., acs.org, doi.org.
58. Swargiary, A., Ivermectin as a promising RNA-dependent RNA polymerase inhibitor and a
therapeutic drug against SARS-CoV2: Evidence from in silico studies, Research
Square, researchsquare.com, doi.org.
59. Tay et al., Nuclear localization of dengue virus (DENV) 1–4 non-structural protein 5;
protection against all 4 DENV serotypes by the inhibitor Ivermectin, Antiviral
Research, sciencedirect.com, doi.org.
60. Udofia et al., In silico studies of selected multi-drug targeting against 3CLpro and nsp12
RNA-dependent RNA-polymerase proteins of SARS-CoV-2 and SARS-CoV, Network Modeling
Analysis in Health Informatics and Bioinformatics, springer.com, doi.org.
61. Uematsu et al., Prophylactic administration of ivermectin attenuates SARS-CoV-2 induced
disease in a Syrian Hamster Model, The Journal of Antibiotics, nature.com, doi.org.
10
62. Umar et al., Inhibitory potentials of ivermectin, nafamostat, and camostat on spike protein
and some nonstructural proteins of SARS-CoV-2: Virtual screening approach, Jurnal Teknologi
Laboratorium, teknolabjournal.com, doi.org.
63. Varghese et al., Discovery of berberine, abamectin and ivermectin as antivirals against
chikungunya and other alphaviruses, Antiviral Research, sciencedirect.com, doi.org.
64. Vottero et al., Computational Prediction of the Interaction of Ivermectin with Fibrinogen,
Molecular Sciences, mdpi.com, doi.org.
65. Wagstaff et al., Ivermectin is a specific inhibitor of importin α/β-mediated nuclear import
able to inhibit replication of HIV-1 and dengue virus, Biochemical
Journal, portlandpress.com, doi.org.
66. Wagstaff (B) et al., An AlphaScreen®-Based Assay for High-Throughput Screening for
Specific Inhibitors of Nuclear Import, SLAS Discovery, sciencedirect.com, doi.org.
67. Yan et al., Anti-inflammatory effects of ivermectin in mouse model of allergic asthma,
Inflammation Research, springer.com, doi.org.
68. Yang et al., The broad spectrum antiviral ivermectin targets the host nuclear transport
importin α/β1 heterodimer, Antiviral Research, sciencedirect.com, doi.org.
69. Yesilbag et al., Ivermectin also inhibits the replication of bovine respiratory viruses (BRSV,
BPIV-3, BoHV-1, BCoV and BVDV) in vitro, Virus Research, sciencedirect.com, doi.org.
70. Zhang et al., Ivermectin inhibits LPS-induced production of inflammatory cytokines and
improves LPS-induced survival in mice, Inflammation Research, springer.com, doi.org.
71. Zhao et al., Identification of the shared gene signatures between pulmonary fibrosis and
pulmonary hypertension using bioinformatics analysis, Frontiers in
Immunology, frontiersin.org, doi.org.
72. Zheng et al., Red blood cell-hitchhiking mediated pulmonary delivery of ivermectin: Effects
of nanoparticle properties, International Journal of Pharmaceutics, sciencedirect.com, doi.org.