Posted on 06/05/2021 4:02:30 PM PDT by nickcarraway
While the focus has been largely on vaccines, you might have also heard Pfizer is trialing a pill to treat COVID-19.
It almost sounds too good to be true. Indeed, the results are very preliminary — but it’s a promising approach.
Where most antiviral agents we’ve tried to treat COVID-19 target the inflammatory and immune response resulting from infection, Pfizer’s pill directly targets SARS-CoV-2 — the virus itself.
Mounting our defense against the virus Much of the illness associated with COVID-19 is due to the intense inflammatory and immune response that can occur with an infection. The most successful treatments so far have targeted this overzealous immune response.
Taken early in the disease, the inhaled corticosteroid budesonide has been shown to reduce the development of more severe disease.
In people hospitalised with COVID-19 requiring oxygen, the oral corticosteroid dexamethasone reduces the likelihood of death.
In the most severe cases — COVID patients admitted to ICU — the anti-inflammatory tocilizumab administered intravenously gives a person a better chance of survival.
But these treatments don’t target SARS-CoV-2 itself; just the consequences of infection. Directly targeting the virus has proven to be more difficult.
Targeting SARS-CoV-2 A virus like SARS-CoV-2 must enter a host cell to reproduce. It does this using its spike protein (a protein on the virus’ surface) to attach to the cell, and then it uses the cell’s own proteins to gain entry.
Once inside the cell, SARS-CoV-2 removes its outer coat and releases its viral RNA (ribonucleic acid, a type of genetic material). This acts as a template, allowing the virus to replicate, and then infect other cells. At any point of this life cycle the virus could be vulnerable to an intervention.
SARS-CoV-2 carries an enzyme, 3C-like protease (3CLpro), which plays a crucial role in the replication process. This protease is almost identical to the protease used by the SARS-CoV-1 (SARS) virus, and similar to the protease used by the Middle Eastern Respiratory Virus (MERS).
So a drug that could effectively target 3CLpro and prevent virus replication could be beneficial against multiple known coronaviruses, and possibly any that emerge in the future.
SARS-CoV-2 uses its spike protein to attatch to a host cell.
Protease inhibitors have been successfully used to treat other viral infections, especially chronic infections such as HIV and hepatitis C.
They were put forward early in the pandemic as a possible treatment for COVID-19. But the HIV drug lopinavir-ritonavir was shown in two clinical trials to be ineffective, with drug levels probably too low to work against SARS-CoV-2. While a higher dose might be effective, it would also likely produce more side effects.
Scientists also proposed a repurposed antiviral drug, remdesevir, originally developed to treat Ebola. Remdesivir delays the ability of the virus to replicate its RNA.
Initial case reports appeared promising and saw the US Food and Drugs Administration approve the drug for emergency use. But the results of randomized controlled trials in hospitalized patients with severe COVID-19 were disappointing.
Although there was a reduction in the duration of illness for patients who survived, it didn’t significantly reduce a person’s chance of dying.
Of course, neither of these agents were designed specifically to target SARS-CoV-2. But in 2020, Pfizer/BioNtech identified a small molecule — PF-00835231 — that blocks the SARS-CoV-2 3CLpro protease. It was originally designed against SARS-CoV-1, but the enzyme in the two viruses is almost identical.
PF-00835231, both alone and in conjunction with remdesevir, appears to reduce the replication of a range of coronaviruses including SARS-CoV-2 in cells in the lab. It also reduced viral replication in a number of animal models, with no adverse safety signals. But it’s important to note this research hasn’t yet been peer reviewed.
What now? Pfizer/BioNtech are taking two drugs to clinical trials for COVID-19: PF-07304814, an intravenous injection for use in patients hospitalised with severe COVID-19 and PF-07321332, an oral agent, or pill, that could potentially be used earlier in the disease. Both are formulations of a 3CLpro inhibitor.
These phase 1 trials, which began in March, represent the earliest stage of drug development. These trials select healthy volunteers and use different doses of the drugs to establish their safety. They also look at whether the drugs elicit sufficient responses in the body to indicate they could be effective against SARS-CoV-2.
The next step would be phase 2 or 3 trials to see if they improve outcomes in COVID-19. Usually this process takes years, but as the pandemic continues to rage globally, Pfizer says it will do this in a matter of months, if phase 1 trials are successful.
The application of antiviral agents in acute COVID-19 has been difficult and unrewarding. Though results are at this stage preliminary, these agents by Pfizer/BioNtech are promising. They could be used early in disease, especially in people poorly protected by vaccination or in those who haven’t been vaccinated.
They could also be used as a means of prevention, to contain outbreaks in exposed people. They should be effective against all the SARS-CoV-2 variants of concern, as well as against other known and possibly emergent coronaviruses.
The Pfizer CEO’s recent suggestion the pill could be available by the end of the year is probably a long shot. But the pandemic has shown us what’s possible in the realm of swift scientific advances, and we’ll watch this space with interest.
Written by Peter Wark, Conjoint Professor, School of Medicine and Public Health, University of Newcastle.
So why not treat it at first symptoms before it becomes severe or acute? It seems like all the clinical trials of therapeutic treatments have been conducted at the late stage of the disease. I think every (or almost every) therapeutic treatment protocol releases in the past 15 months has stressed EARLY ambulatory treatment. If you get to the hospital with advanced hypoxia and/or microthrombosis, you are in deep trouble and will not respond to the therapeutic treatments.
Only to the poorly educated.
We are watching an ongoing crime against humanity by the government public health authorities and Big Pharma.
Yes
Yeah, and the medical industry as a whole is probably the number one cause of death in this country as it is..
How about a cure for BiXiden, Pelousy, Schmuckie, the Burn, AOC, et. al.?
My recipe would be hydroxy, D3 and K2... all harmless but effective.
1. How much D3/day?
2. How much K2/day?
3. What does the K2 do?
Add Dr Berg to each of your questions on Youtube. He keeps himself up to date on all of that stuff. Here is what comes up for K2.
https://www.youtube.com/results?search_query=dr+berg+vitamin+k2
(It’ll be a combination of 10 cent Hydroxy and 10 cent Ivermectin, and they will charge $100 a pill.)
:-)
With some added zinc and Vit D.
Ivermectin 12 mg sold out at many places.
Thank you!
I had not heard of Dr. Berg before reading your comment. I watched his two K2 presentations. He is a good instructor and the information seems to be high quality. Thanks for the link and recommendation.
Colloidal silver. Kills all viruses and bacteria
And you don’t need big pharma. The evil empire from hell.
Screw them
5,000 units of D3
100 mg of K2
promising... hopefully.
Thanks for some guidance.
But I am wondering, what does the K2 do?
https://www.nutraceuticalbusinessreview.com/news/article_page/COVID-19_and_cardiovascular_health_the_role_of_K2_in_high_vitamin_D_supplementation/171381
Regeneron has now been approved by the FDA as an injection. It does not have to be through IV.
Thank you!
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