so there's a few people that keep misunderstanding my core point from my earlier thread, so let me elaborate w/another example from this exact virus.

now, apart from N, E, M & S, which are absolutely required... ...every CoV lineaage has some ersatz collection of optional accessory proteins, that aren't critical for in vitro replication but improve in-host fitness. many are innate immune antagonists targeting either IFN-I or OAS/RNase L, but not all, & most are still poorly understood.

okay, here we go. so as i've said numerous times, DEFUSE could not have given us SARSCoV2 b/c:
1) there is no evidence that WIV had a viable progenitor sequence (something very clearly stated in the ODNI report)
2) it was not funded, i.e. the grant proposal went nowhere 3) it clearly proposed doing FCS insertions into Spike on PSEUDOTYPED LENTIs, i.e. PSEUDOVIRUS

but here's the thing. even if we assume that WIV had a progenitor seq, & taking the most mendacious misinterpretation of DEFUSE possible, it *still* couldn't've resulted in SARSCoV2.

okay... meta-analysis, MDPI special: mdpi.com/1999-4915/15/4… (i love how they proudly display it went from submitted to reviewed to published in a single month). let's check this out...

wait a moment:

https://twitter.com/Antonio_Caramia/status/1649177644976545797

"However, one study accounted for 97.6% of all pooled data."

okay, let's check out ref.#24 then...

(it's journalofinfection.com/article/S0163-…).

"We used nat'l surveillance data to collect info on all SARSCoV2 primary infxn & suspected reinfxn cases between Jan. 2020 until early May 2021."

LMFAO MY GODS WHAT AN ABSOLUTE UTTER TWIT.

https://twitter.com/Tazerface16/status/1649511830652608512

oh my gods the *literal first test burn at this facility* spewed a fuckton of hot debris & ignited a brushfire that chewed up 68 acres of protected wetlands before it could be extinguished: teslarati.com/spacex-starshi…

so i've seen a few well-meaning people try to argue from a point of "accidental lab-origin spillover is impossible" & this really does more harm than good.

short thread, featuring my ex-mathematician self grumbling: why is it bad? b/c it's false. beyond the obvious bad of "i think scientists should stick to making true statements", it's an argument that allows someone to immediately take control of the framing by, i.e. linking documented SARS Classic accidental exposure lab leaks.

incredibly disappointed in this bit from @jwassers, someone whom i expect better of.

this is victim-blamey garbage. like yes, many people are more quiet. many i know aren't active online even, & those who remain self-censor a lot more (yes, myself included).

BUT. *as he rightfully admits*, there is still noise made. there are still stories happening on a constant basis worth covering, & even some of those of visible resistance. "the world's attention has moved on" is being treated as if it is *OUR* fault... & absolves the media of this.

my fav. thing about my youtube account is that if i leave it on autoplay by accident, mute the tab & forget about it, then come back to it like a day later, there's pretty much a 100% chance it's converged onto a playlist entirely made up of electronic organ/Electone remixes. relatedly, this one's pretty nice:

decided to check what exactly is meant by "humanized mice" in the context of studies done at WIV, like i had been assuming that it was mice harbouring human MHC genes & TCR/BCR segments & uhh...

no, it's even dumber. "humanized mice" is just the LL way of saying "hACE2 knockin". like i'm just *boggling* at how the veracity of LLers' claims has already been shredded to sawdust & yet i *STILL* manage to find further absurdities.

almost correct. it's not that gov't underestimated the severity of the pandemic, it's that gov't overestimated their ability to always be able to suppress waves via NPIs alone.

ANYWAY MAYBE NEXT TIME LISTEN TO ALL THE RESEARCHERS YOU HAVE THAT ARE SCREAMING THIS FOR MONTHS.

https://twitter.com/tripperhead/status/1631265753667350533

like you are correct in a sense that a lot of success in 2020/2021 (*OUR* success. *NOT* the gov't's. stop taking the credit when y'all don't fucking deserve any of it) led to complacency & arrogance, ...

congratulations for giving Egaz Moniz & Henry Kissinger a run for the money in the category of "most abhorrently vile person to win a Nobel Prize".

https://twitter.com/MLevitt_NP2013/status/1630569119736111106

i really didn't think the Stanford/GBD set could actually still shock me by their ghoulishness considering all the blood they already have on their hands, but joke's on me it seems, turns out you can always go one stratum of hell lower.

one of the reasons why i push back so strongly on SARSCoV2 origins conspiracy theories is that one thing shared by these people is a massive underappreciation of what nature can do.

i do some synbio & believe me it manages to surprise me *routinely* on even the simplest things. these viruses are out there. sarbecoviruses constantly hop to humans at the interface of humans & wildlife, such as farmers & animal traders. most of these infxns are dead-end. some are not. we have really not even the foggiest of what determines this...

okay this paper *HAS* to be a bit, there's no way anyone would seriously be this insane: pubmed.ncbi.nlm.nih.gov/32813286/ THERE'S MORE THAN ONE OF THESE PAPERS LMFAO WUT: pubmed.ncbi.nlm.nih.gov/33487628/

"...furthermore, the NF-κB inhibitor, GYY4137, ..." *SCREAMING*.

good lord, the "NF-kB inhibitor" compound lists are all wastelands. utter wastelands.

first off, what you *WANT* is an IKKβ inhibitor or at worst a β-TrCP inhibitor. for the first, ML120B HCl is what i use... ...but from what i've seen PS-1145 HCl, TPCA-1 & BMS-345541 are all similarly selective & highly active. for the latter, GS-143 or a rotavirus nsp1 w/the IRF binding site removed both work well.

friend: "have you seen the story of Madame Ping & Guizhong from Genshin yet?"
me: "look you know i neither have time for games nor do i like gacha or RPGs."
"...right. well it's just the story from this update, you have to read it, uhh watch " "& then read the wiki or something, you're good at catching up to plots this way".
"uh... sure, what's so interesting about it anyhow?"
"...i think you'll find it very very relatable"
"uhh sure... *reads*"

that was a day ago. i haven't cried this hard or this often in *years*.

my thoughts on SARSCoV2 variants & the concept of "back to square one": as a 4x vaccinated, never-infected person, i would, if it ever became scientifically necessary, happily be part of a *SARS Classic* human challenge trial. i.e. you're not going to get full antigenic novelty again via just a few mutations at a time, & you need that to get back to 2020. moreover, the degree of conservation in lineage B is sufficiently high (esp. outside of Spike) that i think VE(severe) extends to all sarbecoviruses.

was *another* article on this really necessary, @RetractionWatch? esp. with this tone & title?

retractionwatch.com/2022/12/29/res… i genuinely feel this sort of coverage is a strong disincentive to do the right thing (which was done in this case) in favour of the status quo of *just ignoring the PubPeer complaints*.

honestly reading the unredacted FOIA emails that DREGSTIC likes to hype & honestly my main takeaway is slight surprise at how long @K_G_Andersen & co. entertained silly lab-engineering theories.

at least they correctly rejected them, but still, lol. Fauci: ""puppetmaster"" that both clearly is surprised by & yet doesn't fully understand the role of the "furine cleavage site".

or... non-coronavirologist genuinely baffled. going to go w/the latter.

the study in question is very good, but once again i'm tired of the framing that this is "new" result. orf6 is one of few CoV accessory proteins whose function is unambiguously known. we know how it interacts w/importin α2 & we know how it interacts w/RIG-I 2CARD. furthermore...

https://twitter.com/ejustin46/status/1584495902936338432

adding it to an attenuated MHV genome conveys added pathogenicity in mice: ncbi.nlm.nih.gov/pmc/articles/P… -- of all the SARS Classic accessory genes added this was the only strong signal. we know some details about how: ncbi.nlm.nih.gov/pmc/articles/P…

@juli_bg_bs on the contrary i wasn't pointing out anything exciting but rather something that was behaving as expected. little surprised that BA2.75 escape from bivalent is comparable here but i'd be curious to see that both over a longer period & after a prime/boost on BA.5-specific. @juli_bg_bs like i think a lot of shouting at each other from some people is that -- so from the point of VE(severe) the primary series is highly protective & will be for life/immunosenescence. & apart from the most delusional of the ZC crowd & Xinnie, most will agree pandemic SC2 is over.

@Jayzach421Jay @bencowling88 @VisionOfAsia at this point i'm skeptical intrinsic severity matters *much*... like sure i.e. BA.1 is ""milder"" than Delta intrinsically but the effect from immune memory is so much stronger than this variation that it turns out it has not much effect on outcomes in vaccinated. @Jayzach421Jay @bencowling88 @VisionOfAsia we can debate hypothetical magnitudes of second-order effects all we like, but when the zeroth-order effect is so huge it mostly becomes irrelevant clinically what those second-order magnitudes are.

so regarding nature.com/articles/d4158…, once again it's important to read the paper. the key bit is Figure 2, where this risk was split out by acute care needed for the vax breakthru case: as is now clear, the *vast bulk* of vax breakthru infections in this cohort carry only a slightly increased risk of PASC, if any.

the overall effect is driven basically entirely via the *SEVERE* vax breakthrus.