Comparative analysis of SARS-CoV-2 binding to ACE2 across hundreds of mammalian species reveals the strongest affinity is for *human and primate* ACE2.
Moreover, there is little to no selection pressure toward hACE2 by the virus. It *already worked*.
This is exactly as expected if the viral RBD was chosen from a set of sampled strains based on its affinity for human ACE2.
It is *not* expected for natural origin. That should produce selection toward hACE2 from bat ACE2. Instead, we actually see selection *toward bat ACE2*.
In other words: this random weirdly-shaped Spike RBD was *barely clinging* to its ability to bind bat ACE2 and circulate among bats. It was under selection pressure to bind bat ACE2 better.
Meanwhile it *randomly happened* to have very high affinity for human ACE2 *already*.
The probability of this being coincidence is minuscule. Hardly any humans living nearby have antibodies to SARS-like CoVs. This RBD was not from a human virus.
It came from a low-fitness bat virus that just so happened to be a great candidate for human emergence studies.
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- decide what the word "evidence" means:
a) "clinical results with appropriate sample(s) and endpoints"
b) "what huge lumbering institutions claim ex cathedra with no citations"
c) "what gilead et al. claim"
d) "peer best practices"
- take low-risk bets
If in doubt, *ask the patient*.
People have a fundamental right to participate in their own health-- *they already do so 99% of the time anyway*.
'This might help with X; it's a bit less certain; may cause Y side effects; studies say usually well-tolerated; do you want to try?'
The continued failure to trial or use ITPP in critical care is an indictment against the regulatory and productive institutions of our supposedly-advanced (increasingly just shorthand for 'gridlocked') economy.
Thousands of people already use it for athletic activities.
It has no side effects, is safe at huge doses in animal studies, and has never had a serious adverse event reported in the community ('that's informal' it's post-marketing surveillance..).
The fact that we are jamming tubes down people's throats before giving this, or for that matter even giving cyproheptadine, absolutely disgusts and appalls me.
>Oh that isn't proven
Yes. It. Is.
READ A BOOK; THEY ARE BOTH LITERALLY BASIC PHYSIOLOGY.
>One hope is that the efficacy of the Johnson & Johnson vaccine could rise if it is given as a two-dose regimen.
Obviously, yes! This is much more promising.
Single-dose frankly seems gimmicky, in a very specific sense:
This is effectively just offloading the debate about whether to halfway-dose existing vaccines to a new vaccine candidate instead-- one that has actually been trialed in this dosing schedule.
A couple things about which I would like to be clear, from the now-big account (likely smaller over time):
1) do not ever @/DM to ask where I am or act like I owe you something-- pay me a bitcoin if you want that kind of attention, I know that is pocket change to some of you
2) I have a life outside of COVID-19 and a very, very detailed post history that is approximately two clicks away, depending on your choice of platform access method: search feature, "__ice9 <whatever topic>" papers generally do not become 'out of date' and a result is a result
3) I am frankly a bit bored. The acute disease was obviated months ago by dual entry inhibition. Not my problem if the west ignored it because it came from Iran, or due to statistical illiteracy or vile conflicts of interest (hi Gilead puppets 🎭). Fluvoxamine looks great too.
Side note: strangely demanding PK study; very rigorous protocol. Hope participants were at least paid well. But they got us a number so I am pleased.
NAC may not have a large impact in monotherapy, given only EC50 is hittable (not EC90 except perhaps IV) and gappiness in plasma concentration peaks even q.i.d. (slightly compensated by permanent nature of damage done to exposed Spike copies).