Thread by @ydeigin

1/12

Ok, here goes nothing. Remember this little thing called a furin cleavage site? You know, the one that made SARS2 into a real promiscuous little virus? Well, as some have pointed out before, the strategy of inserting a furin cleavage site was not only

2/12

investigated by coronavirologists previously as a tool to expand virus tropism, but also by other virologists as a tool to actually ATTENUATE a virus. In other words, a vaccine strategy.

Getting goosebumps yet? I am.

3/12

So how could this be a vaccine strategy? Well, the idea, as I understand it, was to take a virus, insert some FCSs into it in key places, but do so in a cell culture that do NOT normally have furin, and thus the virus won’t get cut in such cells. But then if you infect

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an animal with such virus, it will get into the cells, trigger an immune reaction which will produce antibodies, but the virus won’t be able to effectively replicate because the newly created virus proteins will get diced up by furin that is well present in animal cells.

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Sounds great on paper, doesn’t it?

So what’s a good place to insert a new FCS in a coronavirus that won’t affect it too much? I mean, you need the virus to remain viable in culture and infective enough to get into cells. So, any obvious candidate spots?

6/12

Oh, oh, I know! Why not insert it in the Spike, at the spot where other CoVs have one natively, but none of the SARS-like CoVs do? They must not have one for a reason, right? It probably makes them non-viable or something – there’s gotta be evolutionary pressure against it.

7/12

Oh, oh, you know what else we can do to make our vaccine safer? It seems that if we have a polybasic cleavage site like RxRR, then furin normally cuts after RR. So And that is where other proteases normally cleave the S1/S2 junction, even without a FCS –

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after the R already present at the junction. But what if we insert not RxRR, but RRxR? Would that maybe change the cleavage direction, leaving S2 with a little xRR overhang and thus interfering with its membrane fusion and attenuating it further? Worth a try.

9/12

Ok, let’s do a literature search on FCS insertion into viruses. Oh look, there is a 2013 Chinese paper whose authors have done so – they inserted RIRR into their construct.

10/12

Oh, look, there’s CGG coding for the first R. Where did I see it before? Hmm Oh right, in SARS2 where RRAR is coded by CGG CGG GCA CGT.

ncbi.nlm.nih.gov/pmc/articles/P…

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Btw, one of the authors of that paper, Shibo Jiang, has subsequently co-authored a paper in 2015 with Shi Zhengli and Ralph Baric on – guess what – the role of FCS in the tropism of CoVs:

jvi.asm.org/content/89/17/…

12/12

Waaaait a second. So could it be that SARS2 is an undercooked bat virus vaccine candidate that has escaped from a lab??? You know, like that time in 1977 when a temperature-sensitive H1N1 vaccine candidate escaped from a lab and caused a global pandemic?

Holy shit. 💣💥

Oh crap, seems I forgot to mention this nice little patent that I was pointed to by @nicholsonbaker8:

patentimages.storage.googleapis.com/f9/34/81/515c1…