Capitol Hill Blue Forums Science and Technology Health, Medicine & the healing Sciences Medications that might help against SARS-CoV-2

Paxlovid is a combination of something new, PF-07321332, a new protease inhibitor specific for the Covid virus, and something old, Ritinovar, another protease inhibitor that we have been using for years in HAART for treating HIV. It inhibits the breakdown of other protease inhibitors giving them a longer half-life in circulation.

Drug researchers have been mining drugs that we already have, and know about their dosages and side effects/toxicity. Ritinovar was fortuitously found when they were screening known drugs for binding to the spike protein target Angiotensin converting enzyme. It was thought to be a possible treatment for Covid because of it's binding to target. It must not have been very effective, by itself in vitro, but i will look it up.
So, it looks like they found the right drug to pair with PF-07321332 to increase its efficacy, but found it for the wrong reason.

So someone figured it was worth a try, and it does seem to be a game changer in that even if us boosted folks still get infected, there is an oral med that doesnt have the administration problems of the monoclonal cocktails. Of course, the anti-vax game also changes as it is likely that it will be used, similar to DeSantis pushing the monoclonal treatment rather than immunization. The game gets a little more complicated, as now there is evidence that the SARS-COV2 can be reverse transcribed and inserted into cellular DNA. This is being looked into as a possible cause of long Covid, as you can find viral genome in the absence of viral replication.

It would indeed be ironic if the truly deluded Q-types, who are afraid that the government is trying to populate their bodies with micro-robots in vaccines, got their genomes infiltrated and colonized with SARS-COV2, because they avoided the vaccines and ended up with long long Covid.

No doubt someone will consider trying some of the reverse-transcriptase inhibitors that we use for HAART. One problem with that is that RT inhibitors mess with the fidelity of transcription, and when that happens it increases the probability of new mutant variants with new multiple drug resistance.

All the more reason for vaccine mandates, otherwise, what could go worng with moar variants?
TAT

New variants may not be a problem: Even if a new variant mutation occurs, it has to replicate lots and lots of times to get spread to anybody else. Few of those "replications" would be viable if the antiviral drug is still there.

What few people are talking about is that some of these "wonder drugs" may be so effective that the patient may not have enough virus for long enough to gain any immunity. Great for acute treatment, but not so great because the patient can get reinfected within a week after treatment ends. That avoids the "reinfection as booster" phenomenon.

I think the standard medical advice should be to quarantine for a couple weeks and then get vaccinated after an antiviral treatment.,

Very cool paper discussed on TWIV #829 on Youtube. It's about the history of Pfizer's Paxlovid. Seems it's original form was developed almost 20 years ago for SARS1! Development stopped because SARS1 died out and there was nobody to test it on (or to pay for it). When the current pandemic started, researchers pulled it of the dusty shelf and had another look at it. The cool thing is that the viral protease it blocks cuts up corona virus mega-proteins at a specific sequence location. Human proteins don't have any such sequence or such a protease! They went through six different iterations finding a molecule that would retain the original protease inhibitor function, and yet be well absorbed orally. The sixth one did the trick, but in monkeys they found it was inactivated by a cytochrome enzyme in the gut, so they did not get good serum levels. Ritinovar was known to inactivate that cytochrome enzyme, so they tried adding it. It worked! They got very high serum levels. (That's why Ritinovar is used to protect HIV protease inhibitors.)

Then they had to check it for safety. Apparently it does not react with ANY human biochemistry. They were required to give monkeys and rats ridiculously high doses, and found zero adverse effects. Then they ran human drug trials, and it was fantastically effective (given early, of course) with no adverse effects reported. The FDA told them to stop their Phase II/III trials and give the controls the drug, because it worked so well it was unethical to have a control group!

One very nice serendipity: It works against every corona virus, including SARS1, MERS, and all of the corona common cold viruses. And very likely will work against any future corona virus spillover. It's also MUCH easier to make in bulk than vaccines or MABs, and the pills have no special handling requirements. Vaccines are going to be with us for a long time, but this drug will make MABS much less necessary.

Interesting factoid: Ivermection can block the same protease, but it's very hard to get it's levels in infected cells high enough to do that without killing the patients. The fact that this drug has zero interactions with human biochemistry makes it much much safer. Ivermectin interacts with a bunch of stuff, which it's proponents claimed was great but actually causes problems.

Beautiful animation that covers all the immunilogical processes around SARS-COVID2 infection. All to proper scale! It runs just two minutes.

Short Animation Worth Watching

TAT

Excellent video!!!