hoo boy.

this is not a good paper at all. it pains greatly me to have to debunk claims made by a former colleague whom i respected a lot, but... yeah. here we go.
let's just start with this claim, which, excuse me, *what* literature shows that we have the ability to make designer viruses this carefully tailored to any profile we want?
yes, oligonucleotide synthesis nowadays is cheap & comparativrly easy, but what is being implied would require us to have a *FAR* greater understanding of the virology of CoVs than we currently do.
this is meaningless w/o a much larger survey of the accessory protein subgenome of the β-CoV pool than we currently have. other than N/S/M/E/orf3a/orf3b, these are basically mix'n'match, & the presence or absence of any is meaningless.
or...or it literally just means that ZC45/ZXC21 are our closest wild isolates that we have to #SARSCoV2??? like i actually cannot believe i'm reading this paragraph, it's so daft that this argument falls on its face immediately.
this is just embarrassing, Scarlett, you know better than to put your name behind this utter garbage, much less write it yourself.
yes, b/c as you just stated, S1 determines tropism & so is virtually guaranteed to be under high mutational burden within its native host (i.e. Rhinolopus bat) pool. lack of extremely high seq homology is not at all surprising.

see also:
also, before i continue this thread, let me head off an argument i see coming up over&over again: if the bat pool is in the region of Yunnan province, why did it cause an outbreak in Wuhan? well, Wuhan is THE major central mainland transit hub.
it's like asking "if this virus has a regional pool in... i'unno, rural Mississippi, why did the outbreak start at Chicago O'Hare". it doesn't automatically mean lab release, much more likely it's due to high transit density.
OKAY, continuing this thread. so much left and we're not even at Part II yet!

anyhow, not only would nobody engineering a virus nowadays use restriction endonucleases, but you're proposing the restriction sites THEMSELVES were added??? this makes no sense.
i'm just going to skip over the entire section about the polybasic FCS at the S1/S2 junction: Bill Gallagher already explained perfectly well how this can easily arise naturally *weeks ago*: virological.org/t/tackling-rum…
(if anyone has specific questions about that section, ask away, but i'm not going to go thru it point-by-point when the issues are basically the same as the ones trying to justify the Spike RBD as being ""engineered"").

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