Introduction
The discourse surrounding ivermectin’s potential role in COVID-19 treatment has been fraught with polarization and oversimplification. Much of the debate stems from an entrenched mechanistic bias in biomedical research: one that favors clear, single-target interactions over complex, ecological dynamics. Yet in infectious disease, where host–microbe–microbe interactions shape therapeutic outcomes, such reductionism obscures viable clinical avenues. The following commentary challenges that paradigm by illustrating how mechanistic plausibility and patent economics, rather than biological reality, often determine which discoveries advance to the clinic.
Copy and paste of my comments on another thread:
It’s out of character for me to correct misspellings or grammatical errors because it’s pedantic. However, since you admit to marginalizing my position and credibility for this reason, I suppose you have to intellectually tangle with me now that we are on equal footing, then: it’s “label”, not “lable.” You walked yourself into that one.
Now. As far as the use of ivermectin for COVID, as I pointed out before (perhaps not well enough), my interest was in azole-class cholesterol transport inhibitors because, mechanistically, that made sense to target viral replication. Despite innumerable anecdotal accounts of efficacy (which I’m not likely to discredit off-hand) I was not paying enough attention to ivermectin because mechanistically it didn’t make sense to me as a viable drug for repurposing.
Further, while I agree that investigations are not proof, there is something to be said for continued investigations if preclinical in vivo data show promise. So let me explain in a sort of circuitous manner why.
It is possible that although a drug didn’t have a direct effect on the pathogen itself, in vivo, there may have been an additional environmental factor that explains efficacy, or a different target that was hit that allowed greater viral clearance. Keep in mind, there are other relationships at play beyond just the virus itself. There are secondary infections, co-infections, and relationships viruses have with other taxa.
I’ll use gingivitis as an example. Consider that the causal pathogen in gingivitis is p gingivalis. That’s well established. Everyone knows that. However, even en vitro interventions that p gingivalis shows great sensitivity to don’t have the same effect en vivo. In my “practice”, I give fluconazole instead. Mechanistically, fluconazole makes no sense whatsoever against P. gingivalis. However, P. gingivalis evades immune detection in the presence of another pathogen, which is not considered causal in the gingivitis condition. That pathogen is Candida tropicalis or Candida albicans. When Candida is removed, the immune system detects P. gingivalis, and neutrophils get to work to transport or chelate iron and zinc, which cripple the protease activity and siderophore uptake for P. gingivalis. Lo and behold, P. gingivalis is eradicated.
Now, is fluconazole going to get green-lighted for new patents for gingivitis? Not likely. It’s missing direct mechanistic activity against the established causative pathogen. Drug repurposing, especially in infectious diseases, is often viewed through the narrow lens of single-agent, single-pathogen efficacy, which limits patentability and commercial incentive.
So even if in vivo data demonstrates that an antifungal indirectly unmasks a bacterial pathogen to immune clearance, the absence of a clean, direct molecular target makes it nearly impossible to build a strong composition-of-matter claim or method-of-use patent.
This creates a translational gap, which I find infuriating. Compounds that may be clinically effective through ecosystem-level mechanisms or host–pathogen interactions are often left unexplored, not because they lack biological plausibility, but because they lack a clear patent pathway that would justify investment. In the case of fluconazole, you would need a new method of use to garner protections.
So it is unfortunate that many potentially useful repurposed drugs fail not in biology, but in business logic. When efficacy derives from ecological or host–microbe dynamics (like fluconazole’s removal of Candida, enabling immune clearance of P. gingivalis), the absence of a patentable “hook” often ensures the discovery remains in the literature rather than the clinic. This is where my work intersects into this conversation.
But for the sake of staying on topic, my point is that I would not discount ivermectin on the basis that its activity during a COVID infection could not be mechanistically explained at the time. Or because it did not directly target it. It is entirely possible that ivermectin exerted its effects by modulating another target that indirectly reduced barriers to viral clearance. Such mechanisms would not be captured by in vitro assays focused solely on viral replication, yet could still be clinically meaningful in vivo.
In that sense, while the anecdotal evidence for ivermectin must be weighed cautiously, it is not implausible that its observed effects arose from another ecological or host–microbe interactions rather than a direct antiviral mechanism. So the lack of patents doesn’t prove that ivermectin lacked effect. It may prove that its effects (if they occurred) were mediated through indirect ecological dynamics that don’t fit neatly into a patent model.