Originally Posted by
Chris_Halkides
To do a full analysis of the Campbell video, one would need to read the papers.
Indeed. There's links to all of them in the video description. At least he's usually pretty good in that respect. So here's my attempt to review each of his cited papers:
OK,
the first link is to the Pfizer press release about their new drug. No evidence for Ivermectin there.
The second link:
Identification of SARS-CoV-2 3CL Protease Inhibitors by a Quantitative High-Throughput Screening
I can't even find the word Ivermectin appearing anywhere in this paper.
Quote:
We performed a quantitative high-throughput screening (qHTS) of 10 755 compounds consisting of approved and investigational drugs, and bioactive compounds using a SARS-CoV-2 3CLpro assay. Twenty-three small molecule inhibitors of SARS-CoV-2 3CLpro have been identified with IC50s ranging from 0.26 to 28.85 μM. Walrycin B (IC50 = 0.26 μM), hydroxocobalamin (IC50 = 3.29 μM), suramin sodium (IC50 = 6.5 μM), Z-DEVD-FMK (IC50 = 6.81 μM), LLL-12 (IC50 = 9.84 μM), and Z-FA-FMK (IC50 = 11.39 μM) are the most potent 3CLpro inhibitors. The activity of the anti-SARS-CoV-2 viral infection was confirmed in 7 of 23 compounds using a SARS-CoV-2 cytopathic effect assay. The results demonstrated a set of SARS-CoV-2 3CLpro inhibitors that may have potential for further clinical evaluation as part of drug combination therapies to treating COVID-19 patients and as starting points for chemistry optimization for new drug development.
Was Ivermectin among the 10,755 compounds they screened? It does not appear to be among those which they call the "most potent". Nor does that word appear anywhere in the paper as far as I can tell.
BTW, those compounds were:
Quote:
A primary screen of 10 755 compounds in the libraries containing approved drugs, investigational drug candidates, and bioactive compounds yielded 161 hits in which the hit rate was 1.5% (Figure S1).
The next link, now we finally get a paper about Ivermectin:
Microscopic interactions between ivermectin and key human and viral proteins involved in SARS-CoV-2 infection
But it's all about a computer simulation. It's way too technical for me to understand, but I was able to discern that it is about a computer model of how these molecules would interact.
Next link:
Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents
Seems like promising
early-stage research, involving in vitro testing as well as computer simulations. It's very technical, but it doesn't involve any actual clinical trial of ivermectin in patients.
Quote:
in this study, we have reported that ivermectin inhibits the enzymatic activity of SARS-CoV-2 3CLpro and thus may potentially inhibit the replication of RNA viruses including SARS-CoV-2. These studies suggest that ivermectin could be a potential drug candidate to inhibit the SARS-CoV-2 replication and the proposed anti-viral mechanism of ivermectin presented in Fig. 8 and in vivo efficacy of ivermectin towards COVID-19 is currently been evaluated in clinical trials
So the paper is far from claiming that ivermectin would actually be a clinically effective therapeutic.
Next link:
Ilimaquinone (marine sponge metabolite) as a novel inhibitor of SARS-CoV-2 key target proteins in comparison with suggested COVID-19 drugs: designing, docking and molecular dynamics simulation study
Quote:
In the present study, the inhibitory prospects of ilimaquinone (marine sponge metabolite) were assessed in comparison with hydroxychloroquine, azithromycin, favipiravir, ivermectin and remdesivir at the active binding pockets of nine different vital SARS-CoV-2 target proteins (spike receptor binding domain, RNA-dependent RNA polymerase, Nsp10, Nsp13, Nsp14, Nsp15, Nsp16, main protease, and papain-like-protease), employing an in silico molecular interaction based approach. In addition, molecular dynamics (MD) simulations of the SARS-CoV-2 papain-like protease (PLpro)–ilimaquinone complex were also carried out to calculate various structural parameters including root mean square fluctuation (RMSF), root mean square deviation (RMSD), radius of gyration (Rg) and hydrogen bond interactions.
So another paper using computer-based modeling. Campbell keys in on this quote:
Quote:
From the docking analysis, ivermectin showed the highest docking score with an average energy of −8.5 kcal mol−1 among all the compounds. Remdesivir showed the lowest binding energy and highest docking score of −9.9 kcal mol−1
He admits he doesn't really understand this, but thinks this means ivermectin is better than Remdesivir.
I have absolutely no idea, and I doubt that most of his audience does either.
The
next link is only available to users in the United Kingdom, so I'll skip it. (that's not the link, it's the URL I got redirected to)
Next link:
Exploring the binding efficacy of ivermectin against the key proteins of SARS-CoV-2 pathogenesis: an in silico approach
More computer modeling.
The next link is the Pfizer press release again.
And finally:
Molecular Docking Reveals Ivermectin and Remdesivir as Potential Repurposed Drugs Against SARS-CoV-2
Quote:
Molecular docking of these drugs with different SARS-CoV-2 target proteins, including spike and membrane proteins, RdRp, nucleoproteins, viral proteases, and nsp14, was performed. Moreover, the binding affinities of the human ACE-2 receptor and TMPRSS2 to the different drugs were evaluated. Molecular dynamics simulation and MM-PBSA calculation were also conducted. Ivermectin and remdesivir were found to be the most promising drugs. Our results suggest that both these drugs utilize different mechanisms at the entry and post-entry stages and could be considered potential inhibitors of SARS-CoV-2 replication.
Right. So that's all of the links that I could access.
No clinical trials, just early-stage drug discovery research.
Quote:
I got about halfway through the video, and one thing that jumped out at me was that one of the papers was using ivermectin at 50 µM in concentration. It gave substantial but not complete inhibition. That does not strike me as being anywhere near good enough affinity. Another thing: docking is a useful, in silico tool, but it is no substitute for measuring the affinity properly. Given that ivermectin and remdesivir bind to different enzymes altogether, I don't see the point of comparing their docking affinities.
EDT
I got all the way through. One problem is that he is taking docking studies, which are done in silico, way too seriously. I am not an expert in docking, however.
I come to the same conclusions, but I too am not an expert. No clinical trials, mostly computer-based modeling and hypothesizing.
But the way he packages this stuff, it's as if it proves that Ivermectin is just as effective as Paxlovid, but none of this shows anything like that. Actually clinical studies are needed to prove that, and the ones that have been done (the ones not fraudulent anyway) did not find a similar therapeutic effect.