#22: Ivermectin and its Mechanisms of Action
Turns out, there's a whole lot to the "horse paste" that warrants attention.
Hello All,
I’ve mentioned early treatment in prior posts, but I’ve yet to do a dedicated take on any treatments in particular. Why not start with the media’s favorite “horse paste”? (If you don’t know where that reference comes from, I’ll get there!)
As always, I am no doctor and nothing here should be considered medical advice. But a very detailed article in The Journal of Antibiotics is worthy of attention here:
The mechanisms of action of ivermectin against SARS-CoV-2—an extensive review by Asiya Kamber Zaidi & Puya Dehgani-Mobaraki
Ivermectin has a long history, which admittedly I knew nothing about prior to COVID. For an intro summary, I leaned on this article here. Ivermectin belongs to a group of “avermectins” - which, according to Pharmaceuticals article, “are a group of drugs that occurs naturally as a product of fermenting Streptomyces avermitilis, an actinomycetes, isolated from the soil… Avermectins are generally used as a pesticide for the treatment of pests and parasitic worms as a result of their anthelmintic and insecticidal properties. Additionally, they possess anticancer, anti-diabetic, antiviral, antifungal, and are used for treatment of several metabolic disorders.”
The “horse paste” reference is in jest, as ivermectin was subject to much controversy in the media earlier this year. Major media described it as a “anti-parasitic drug used for livestock” - which is true, but it depends on the dosage/delivery. There are established dosages for humans, obviously. Just ask Joe Rogan!
In terms of its earlier uses, Ivermectin has “radically” lowered the incidence of river blindness and lymphatic filariasis, which back in 2015 earned its discoverers/developers the Nobel Prize in Physiology or Medicine. A little more than just an anti-parasitic drug for livestock, eh?
In the COVID pandemic, ivermectin was one of the existing drugs that received much attention as a possible tool against the virus. “Drug repurposing” involves identifying new uses for existing drugs (like ivermectin for COVID-19 patients) - and compared to new drugs which are expensive to develop and difficult to assess for safety/risk profiles, repurposed drugs have the advantage of affordability and years of health and dosage history behind them.
It has always perplexed me - in a pandemic situation, where our health and public authorities are constantly making choices “for our health and safety” - why we wouldn’t explore safe and affordable drugs if they were proven to help people.
But you can’t claim something is helpful without evidence, and that’s where the Journal of Antibiotics article comes in. As the article explains (in long, step-by-step detail), ivermectin has many possible mechanisms of action against COVID-19. The authors divide these into four groups of target activity (modified from the article below):
The role of ivermectin against the SARS-CoV-2 virus
A. Direct action on SARS-CoV-2
Level 1: Action on SARS-CoV-2 cell entry.
Level 2: Action on importin (IMP) superfamily.
Level 3: Action as an ionophore.
B. Action on host targets important for viral replication
Level 4: Action as an antiviral.
Level 5: Action on viral replication and assembly.
Level 6: Action on posttranslational processing of viral polyproteins.
Level 7: Action on karyopherin (KPNA/KPNB) receptors.
C. Action on host targets important for inflammation
Level 8: Action on interferon (INF) levels.
Level 9: Action on Toll-like receptors (TLRs).
Level 10: Action on nuclear factor-κB (NF-κB) pathway.
Level 11: Action on the JAK-STAT pathway, PAI-1, that could be involved with COVID-19 sequalae.
Level 12: Action on P21 activated kinase 1 (PAK1).
Level 13: Action on interleukin-6 (IL-6) levels.
Level 14: Action on allosteric modulation of P2X4 receptor.
Level 15: Action on high mobility group box 1 (HMGB1).
Level 16: Action as an immunomodulator on lung tissue and olfaction.
Level 17: Action as an anti-inflammatory.
D. Action on other host targets
Level 18: Action on plasmin and annexin A2.
Level 19: Action on CD 147 on the red blood cell (RBC).
Level 20: Action on mitochondrial ATP under hypoxia on cardiac function.
The direct “antiviral targets” may be useful in the early stages while the anti-inflammatory targets might be addressed in the later stages of the disease.
Each of these levels of action are described in detail within the article, with links to supporting studies. The science is deep and very technical - and each level is worthy of its own analysis. As for the authors’ conclusions, they look forward to clinical results to prove whether or not the mechanisms of action for ivermectin play a role in prevention and treatment of COVID-19. In other words, there is solid support for individual mechanisms of action - but let’s see everything wrapped-up in clinical results.
My posts are intended to be quick reads that cover the highlights, so I will leave the heavy-lifting to the authors themselves - but needless to say, the list of possible mechanisms of action is impressive and worthy of attention. I share it with you here to demonstrate that there is much more to the media’s favorite “horse paste” than most will ever know! We will see what comes from clinical trials, but the analysis was impressively detailed and impossible to ignore for those of us interested in effective early treatments.
Anecdotally, I know people who have taken ivermectin once testing positive with COVID. One in particular jumped on things early, using ivermectin as prescribed by America's Frontline Doctors. This individual experienced no fever and no breathing issues - and after a week of rest and recuperation, tested negative and moved on with life. Of course, this is one experience - results may vary. But based on the extensive Journal of Antibiotics article, there are many possible reasons why this experience was a positive one. Again, results in a controlled study could go a long way toward demonstrating this on a bigger scale.
And so I ask - if there are early treatments out there, such as ivermectin with 20 possible mechanisms of action against COVID-19 - why aren’t they being breathlessly explored by our public health system?
Yes, we hear plenty about vaccines - those of us that haven’t taken them face an almost daily onslaught of pressure to get them. In fact, in Chicago they will soon become a precondition for entering restaurants, bars, gyms and indoor venues (see below).
Alas, this is the world we find ourselves in. Repurposed drugs with long records of safe usage in humans are marginalized (despite increasing evidence of their possible mechanisms of action), while vaccines are pushed relentlessly - to the point where cities are willing to cut off their residents from society and fire frontline workers for not taking them. Oh, and natural immunity is still largely ignored/marginalized (despite the evidence we’ve reviewed here - Brownstone Institute is up to 140 studies in support!).
I, for one, find these kind of policies extremely disappointing - they go against common sense and compassion. Especially when we’ve seen the evidence of viral loads/transmission being the similar between vaccinated and unvaccinated. Vaccine passports are wrong, and they don’t make sense - this isn’t my opinion, it’s what researchers are proving. Yet the Biden Administration has adopted similarly divisive, narrowly-focused messaging throughout, singling out the unvaccinated and ignoring natural immunity. Check out the message coming from the White House right before the holidays:
A winter of “severe illness and death" for the unvaccinated - Merry Christmas and Happy Holidays from the administration! Thankfully, we’ve looked at a lot of evidence that says otherwise on this blog. And for those who don’t have naturally immunity, there is ever-increasing support for early treatments if you do get sick from COVID-19. As I mentioned, there are resources to explore - such as America’s Frontline Doctors.
If only we all focused on helping each other, instead of fear-mongering and dividing based on vaccination status. How about that for a Christmas wish?
Thanks for reading - more to come!
-G
Edit: The original post mentioned "Nature" as the publishing journal, instead of "The Journal of Antibiotics" as is listed in the link. My apologies, this has been corrected!