The fated death of Paxlovid
And Pfizer amazing foretelling skils.
Viral Kinetics of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) Omicron Infection in mRNA-Vaccinated Individuals Treated and Not Treated with Nirmatrelvir-Ritonavir
Oh, this paper is juicy. Not only do we get closer to the real rebound rate (which I estimate is probably up in the 70%+), but I get an answer I have been looking for. Viral load in rebound people is akin to ACUTE CASES.
At this point, after reading my Substack, you are probably aware that this increase in viral load, further depletion of important nutrients, and a rebound that mimics acute cases is not the best thing you should look for. Not only that, a rebound basically guarantees recombination inside the host, therefore leading tooooooooooooo…
Another paper predicts the rise of, in this particular case, a rare yet natural mutation, meaning the virus can naturally achieve it without pressure from the drug itself. It is a mutation to keep in your mind because if only this one pops up, it already dramatically reduces the effectiveness of Paxlovid.
Multiple pathways for SARS-CoV-2 resistance to nirmatrelvir
Transmissible SARS-CoV-2 variants with resistance to clinical protease inhibitors
While Paxlovid is already proving useful in blunting SARS-CoV-2 disease pathogenesis, the long-term consequences of its wide-spread prescription are unknown. Resistance is a major concern given the relatively rapid rates at which SARS-CoV-2 is changing (Alpha, Beta, Delta, Omicron, etc) and the fact that the potency of nirmatrelvir and ensitrelvir varies widely against other coronavirus species (14). For instance, the main proteases of the human α-coronaviruses NL63 and 229E are less susceptible to these drugs suggesting that natural mechanisms of resistance are indeed possible and may already exist in nature (12, 15). In addition, during the clinical development of Paxlovid, the murine coronavirus MHV was used to study nirmatrelvir resistance (https://www.fda.gov/media/155050/download). One of the selected amino acid changes, S144A, causes a >90-fold reduction in the binding efficacy of nirmatrelvir to recombinant Mpro in vitro. To our knowledge, this mutant has yet to be assessed in cellular assay or animal models.
Our results combine to demonstrate that multiple drug resistance mutations already exist in transmissible isolates of SARS-CoV-2 in the global population. However, the longer-term view remains optimistic given our observations of differential drug susceptibilities, which suggests that future compounds may be developed to avoid cross-resistance and help combat the COVID-19 pandemic and future coronavirus outbreaks.
A deluge of papers lately all pointing towards the obvious. Resistance to Paxlovid will come, especially because it is often prescribed as a single treatment, and we will enter another eternal hamster wheel chase, virus evolve to evade or resist a drug, we catch up, commit the same avoidable mistakes, repeat ad infinitum.
Sometimes it truly feels like someone consulted the utmost expert in coronaviruses research, asked him what the world should not do in a SARS-like viral pandemic, and decided at the last moment:
“Let us do everything the expert said, but in reverse.”
No change until some level of catastrophe happens I guess. Did you ever wanted a visualization of the virus when faced with every single proposed strategy implemented so far ?
Sadly viral evolution is not “static” and “linear”, and the widespread use of a single mode of action drug will have consequences beyond mere resistance to that drug. And since we are talking about Pfizer here.
Given the amount of data Pfizer and other Big Pharma companies are gathering, it is pretty easy to forecast and make acquisitions of certain biotech, niche companies to maximize profit and minimize research effort.
And I won’t be my usual me. Here, the only treatment for Sickle Cell Disease is a transplant of a certain kind. I am sure you can put two and two together, right aboooooout…now.
Lol all I can come up with now is "that sucks."
Bone marrow transplant?