What makes Ivermectin a kick-ass antiviral?

This article is updated on Jan 13, 2023.

Ivermectin is the I in all the prevention and treatment protocols of the Front Line COVID-19 Critical Care Alliance.

I-CARE – Early Outpatient Treatment Protocol for COVID-19
I-PREVENT – Prevention & At-Home Treatment Mass Distribution Protocol for COVID-19, Influenza and PSV Protection Protocol
MATH+ – Hospital Treatment Protocol for COVID-19 (Ivermectin included in the protocol)
I-RECOVER – Management Protocol for Long Haul COVID-19 Syndrome (LHCS)
I-RECOVER – Post-Vaccine Treatment

Ivermectin is in all the protocols not only because it is an anti-inflammatory, but it’s also an excellent antiviral.

Mechanism of Action of Ivermectin

Basic science: Cells are made of an inner nucleus surrounded by the cytoplasm, and a wall separates the nucleus and the cytoplasm.

Viruses must enter the nucleus to use the nucleus’s machinery to replicate or multiply. To enter, viruses need to hitch a ride on transport proteins.

SARS-CoV-2 needs to bind with Importin α and with Importin β. The SARS-CoV-2-IMPα/β complex passes through the nuclear wall’s nuclear pore complex (NPC) to enter the nucleus.

Once inside the nucleus, the SARS-CoV-2 replicates in the millions or billions, and succeeding generations enter other host cells to continue replicating.

The immune system has to overcome SARS-CoV-2, and in most cases, the body’s defenses win.

However, in some people with comorbidities like obesity, hypertension, and diabetes, the immune response overreacts to induce a cytokine storm that leads to multi-organ inflammation and dysfunction.

Ivermectin stops entry to the. nucleus

The SARS-CoV-2 can manipulate the host’s immune response to ensure its survival. They do it by binding to the protein in the cytoplasm that transports them into the nucleus.

Once inside, the SARS-CoV-2 proteins reduce the antiviral response, which leads to infection.

In a study by Caly et al., ivermectin binds to the transport protein, Importin α, to prevent the SARS-CoV-2-IMP α/β from forming. This prevents the entry of viral proteins into the nucleus, and the immune system can continue to fend off the virus.

Stopping viral replication means low viral loads. Preventing a hyperimmune response like a cytokine storm exemplified by Acute Respiratory Distress Syndrome or ARDS typically seen in severe COVID-19.

ARDS is when the lungs get flooded with fluid, and the blood oxygen level decreases. Once it happens, the prognosis is poor, even with mechanical ventilation.

From: Caly L et al. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res. 2020 Jun;178:104787

The image above shows the ivermectin blocking the attachment of coronavirus protein to the Importin α transport protein and the nuclear pore complex of the nucleus preventing viral protein entry and leading to an appropriate antiviral response. The following is the figure’s description by Caly L et al.

Schematic of ivermectin’s proposed antiviral action on coronavirus. 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 destabilises 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.

Ivermectin works on the host

Other antibiotics like penicillin act on invading bacteria, and those bacteria can then counter the antibiotics by developing beta-lactamase enzymes to become resistant to antibiotics.

On the other hand, ivermectin works on the host’s cells. That means no viral resistance happens even if a person uses ivermectin for a long time. That is why ivermectin can be used for prevention for a long time.

Even if the SARS-CoV-2 mutates to other variants, the ivermectin will still work!

The other good news is that ivermectin is not only specific to SARS-CoV-2 but also has antiviral activity against other nasty viruses.

Ivermectin inhibits several SARS-CoV-2 enzymes.

An in-silico study by Choudhury and colleagues [6] showed that,

Ivermectin was found as a blocker of viral replicase, protease and human TMPRSS2, which could be the biophysical basis behind its antiviral efficiency.

The antiviral action and ADMET profile of ivermectin was on par with the currently used anticorona drugs such as hydroxychloroquine and remdesivir. [6]

Ivermectin’s actions prevent the entry of SARS-CoV-2 and reproduction into the cells.

Ivermectin has shown antiviral effects on the following viruses:

Yellow fever virus
West Nile virus
Dengue virus
Respiratory Syncytial Virus (common cold virus)
Hendra virus
Newcastle virus
Venezuelan Equine encephalitis virus
Chikungunya virus
Semliki forest virus
Sindbis virus
Influenza, including the super scary Avian influenza A virus (H5N1)
Human Immunodeficiency Type 1 virus
Pseudorabies virus
BK Polyomavirus
Porcine reproductive and respiratory syndrome virus.
SARS-CoV-2 and other coronaviruses and variants

Is Ivermectin Safe?

Ivermectin is one of the safest drugs in the world. A meta-analysis showed that:

A descriptive analysis of these clinical trials for a variety of indications showed no difference in the severity of the adverse events between standard (up to 400 μg/kg) and higher doses of ivermectin.[4]

Note: 400 ug/kg = 0.4 mg/kg

The FLCCC protocol doses are from 0.2mg/kg to 0.4 mg/kg.

Ivermectin is FDA-approved for humans for parasite treatment.

From the FDA website about ivermectin:

Ivermectin tablets are approved by the FDA to treat people with intestinal strongyloidiasis and onchocerciasis, two conditions caused by parasitic worms. In addition, some topical (on the skin) forms of ivermectin are approved to treat external parasites like head lice and for skin conditions such as rosacea.

In Africa, Ivermectin has been prescribed for human filariasis and river blindness for several decades now. The use of ivermectin worldwide has been a Godsend because these parasitic infections cause physical deformities.

I discussed ivermectin in Africa in – Solved! The Ivermectin African Enigma

Furthermore, ivermectin is inexpensive. Drugs.com says a 3 mg dose of ivermectin is $4.70. Compare that to Paxlovid at $120 per dose.

Another thing about Paxlovid is that COVID-19 tends to come back after taking it. I discussed that at The Paxlovid Rebound Study. That is because – Paxlovid blunts the adaptive immune response to SARS-CoV-2

The cost for a molnupiravir oral capsule of 200 mg is around $10 for a supply of 40 capsules. However, users, especially the immune-compromised, may run the risk of producing more SARS-CoV-2 variants. Molnupiravir Causes Hundred of SARS-CoV-2 Mutations.

Ivermectin is an Essential Medicine

Ivermectin is included on the WHO model list of essential medicines. And thus widely available.

No surprise that the discoverers of ivermectin, William C. Campbell and Satoshi Ōmura, won the Nobel Prize for Medicine in 2015.

NIH stand on ivermectin is neutral

Despite the evidence about ivermectin’s effectiveness against COVID-19, the NIH COVID-19 Treatment Guidelines, on Feb 11, 2021, states:

There is insufficient evidence for the COVID-19 Treatment Guidelines Panel (the Panel) to recommend either for or against the use of ivermectin for the treatment of COVID-19.

Off-label use

Some may argue that ivermectin is not FDA-approved for COVID-19. However, it is common practice in clinical medicine to use medications outside the FDA approval, called off-label use.

An example of off-label use is tamsulosin or finasteride in those with kidney stones in males and women. Both medicines are FDA-approved for prostate enlargement and not for kidney stones. Women, as you may know, do not have prostates. However, that is an acceptable use.

Anyone who has suffered the agony of a kidney stone colic will probably accept the off-label use.

Here is what the FDA has to say about “off-label” use:

Why might an approved drug be used for an unapproved use?

From the FDA perspective, once the FDA approves a drug, healthcare providers generally may prescribe the drug for an unapproved use when they judge that it is medically appropriate for their patient.

Recall that the FDA has already approved ivermectin. Their primary job is to find out that prescription drugs are safe.

If you are thinking of using ivermectin, talk to your physician, and refer them to the prevention and treatment protocols of the Front Line COVID-19 Critical Care Alliance.

Knowledge about Covid-19 is rapidly evolving. Information may update as new studies are made. Stay current by subscribing. Feel free to share and like.

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References:

Caly L, Druce JD, Catton MG, Jans DA, Wagstaff KM. The FDA-approved drug ivermectin inhibits the replication of SARS-CoV-2 in vitro. Antiviral Res. 2020 Jun;178:104787. doi: 10.1016/j.antiviral.2020.104787. Epub 2020 Apr 3. PMID: 32251768; PMCID: PMC7129059.
Caly L, Wagstaff KM, Jans DA. Nuclear trafficking of proteins from RNA viruses: potential target for antivirals? Antiviral Res. 2012 Sep;95(3):202-6. doi: 10.1016/j.antiviral.2012.06.008. Epub 2012 Jun 28. PMID: 22750233.
Heidary F, Gharebaghi R. Ivermectin: a systematic review from antiviral effects to COVID-19 complementary regimen. J Antibiot (Tokyo). 2020;73(9):593-602. doi:10.1038/s41429-020-0336-z
Miriam Navarro, Daniel Camprubí, Ana Requena-Méndez, Dora Buonfrate, Giovanni Giorli, Joseph Kamgno, Jacques Gardon, Michel Boussinesq, Jose Muñoz, Alejandro Krolewiecki, Safety of high-dose ivermectin: a systematic review and meta-analysis. Journal of Antimicrobial Chemotherapy, Volume 75, Issue 4, April 2020, Pages 827–834, https://doi.org/10.1093/jac/dkz524.
Kory, Pierre MD^1,*; Meduri, Gianfranco Umberto MD²; Varon, Joseph MD³; Iglesias, Jose DO⁴; Marik, Paul E. MD. Review of the Emerging Evidence Demonstrating the Efficacy of Ivermectin in the Prophylaxis and Treatment of COVID-19, American Journal of Therapeutics: May/June 2021 – Volume 28 – Issue 3 – p e299-e318 doi: 10.1097/MJT.0000000000001377
Choudhury A, Das NC, Patra R, et al. Exploring the binding efficacy of ivermectin against the key proteins of SARS-CoV-2 pathogenesis: an in silico approach. Future Virol. 2021;10.2217/fvl-2020-0342. doi:10.2217/fvl-2020-0342

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