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Dr. John Campbell created a video in which he claims to have demonstrated that Ivermectin has the same pharmacodynamic modality of action as the new Pfizer antiviral PF-07321332, which inhibits the 3CL main protease of SARS-Cov-2. In this video I address Dr. Campbell's misunderstandings and show that the biochemical mechanism he claims is not well supported by data, that his interpretations are based on misundertandings of the literature, and that -- even if ivermectin inhibits the 3CL protease exactly as he describes in biochemical assays -- Ivermectin cannot achieve the corresponding pharmacodynamic effect because the highest possible concentration in the human body is several orders of magnitude too low.

Dr. Campbell's basic misunderstandings of the biochemistry, as well as his evident failure to grasp the differences between a biochemical effect and a pharmacodynamic effect, are consequential in a pandemic because of his enormous influence on this platform.

ERRATUM
There was a verbal slip-up when discussing Table 2 of the fourth paper when I mistakenly said in passing that remdesivir had the best predicted binding to 3CL protease according to Table 2. It does not: ivermectin has the best predcited binding of the compounds to 3CL protease (-7.7 kcal/mol compared to remdesivir's -7.1). I was going to make a joke that "In his defense, Dr. Campbell was accidentally correct about the relative order in this case" but I slipped up when making the larger point. To avoid any confusion, I'd deleted that second or two of video and apologise for the error. Dr. Campbell's misinterpretation of that table remains unchanged.

CHAPTERS
00:00 Introduction
04:23 Who am I to criticise Dr. Campbell?
07:53 Dr. Campbell's central claim
09:10 The drugs
14:21 The target (SARS-Cov-2 3CL main protease)
19:38 Identification of SARS-CoV‑2 3CL Protease Inhibitors by a Quantitative High-Throughput Screening (https://pubs.acs.org/doi/abs/10.1021/...)
34:23 Microscopic interactions between ivermectin and key human and viral proteins involved in SARS-CoV-2 infection https://pubs.rsc.org/en/content/artic...
44:47 Identification of 3-chymotrypsin like protease (3CLPro) inhibitors as potential anti-SARS-CoV-2 agents https://www.nature.com/articles/s4200...
1:01:30 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 https://pubs.rsc.org/en/content/artic...
1:10:45 Exploring the binding efficacy of ivermectin against the key proteins of SARS-CoV-2 pathogenesis: an in silico approach https://www.futuremedicine.com/doi/10...
1:13:50 Closing remarks

DISCLAIMER
This video is for educational purposes only.
DECLARATION
I have no conflicts of interest. I do not receive any funding or compensation from anyone making or developing treatments for Covid-19, including vaccines or antivirals. This video will never be monetised.

RESOURCES AND ADDITIONAL REFERENCES
- Dr. Campbell's original video    • New Pfizer drug and ivermectin  
- A response to Dr. Campbell by Dr. Susan Oliver    • Science mistakes made by ivermectin f...  
- Video on high throughput screening    • High Throughput Screening  
- SARS-Cov-2 assays from the NIH's National Center for Advancing Translational Sciences https://opendata.ncats.nih.gov/covid1...
- Zhao, Y., Fang, C., Zhang, Q. et al. Crystal structure of SARS-CoV-2 main protease in complex with protease inhibitor PF-07321332. Protein Cell (2021). https://doi.org/10.1007/s13238-021-00...
- The Pharmacokinetics and Interactions of Ivermectin in Humans—A Mini-review https://www.ncbi.nlm.nih.gov/pmc/arti...
- Considerations for the discovery and development of 3-chymotrypsin-like cysteine protease inhibitors targeting SARS-CoV-2 infection https://pubmed.ncbi.nlm.nih.gov/34029...
- Glutamate-gated chloride channels and the mode of action of the avermectin/milbemycin anthelmintics https://pubmed.ncbi.nlm.nih.gov/16569...
- Ivermectin and its target molecules: shared and unique modulation mechanisms of ion channels and receptors by ivermectin https://www.ncbi.nlm.nih.gov/pmc/arti...
- Mode of action of ivermectin https://link.springer.com/chapter/10....
- Ivermectin as a potential COVID-19 treatment from the pharmacokinetic point of view: antiviral levels are not likely attainable with known dosing regimens https://www.tandfonline.com/doi/full/...
- Pharmacokinetic considerations on the repurposing of ivermectin for treatment of COVID-19 https://bpspubs.onlinelibrary.wiley.c...
- Toxic Effects from Ivermectin Use Associated with Prevention and Treatment of Covid-19 https://www.nejm.org/doi/10.1056/NEJM...