Buckle up: SARS2 is improving its Furin cleavage site

What you see with the highly pathogenic influenza viruses we humans produce in our factory farms, where we put sickly deformed chickens together in cages so that the viruses have no need to keep their host alive, is that they end up with a big polybasic Furin cleavage site. That’s part of what makes them so deadly.

All human cells produce small amounts of Furin, so it makes it easy for viruses to get their proteins produced for them when they have a site where Furin binds. This allows these influenza viruses to infect many more cell types than they otherwise could, thereby making them deadlier than the regular influenza normally transmitted by wild migratory birds.

What does such a Furin cleavage site look like? Six or seven Arginines and Lysines:

Furin is ubiquitously expressed in the Golgi apparatus of all cells,5 but generally only at low levels. Furin has a well known role in viral pathogenesis and efficiently cleaves polybasic or multi-basic sites such as those found in influenza virus subtypes H5 and H7. These highly pathogenic avian influenza viruses have therefore served as a model for the role of furin cleavage as a viral virulence factor. Mechanistically, this furin site is created through polymerase slippage during replication and occurs at the interface of the HA1 and HA2 subdomains. Such polybasic sites typically exist as a stretch of 6–7 arginine and lysine residues (eg, RKKRKR|G) that can be efficiently cleaved by furin, thereby allowing systemic spread based on the ubiquitous expression of the protease.6 Without the polybasic cleavage site, infection is restricted on the basis of the localised presence of the trypsin-like proteases activating low pathogenicity influenza viruses. Other influenza viruses (such as H9) modulate the cleavage site sequence through mutation and recombination.

As most people now know, SARS2 has a mysterious Furin cleavage site, that the other viruses in its family don’t have. Many people see this as evidence it came from a lab, but I think there is better evidence for that assertion than the Furin cleavage site.

Either way, what some of you will know is that the SARS2 Furin cleavage site is unusual. Not just for the nucleotides it uses to arrive at Arginine, but also for its unorthodox structure. There are much better ways to make a Furin cleavage site. But with the new BA.2.86 variant, it’s now rapidly improving its Furin cleavage site.

The first improvement to its Furin cleavage site was P681R, which helped make the Delta variant so deadly. It turns a Proline into an Arginine, giving it more Arginines next to each other, making it better at attracting Furin to do its job for it. Omicron lost this improvement, but now the new BA.2.86 has that improvement again.

But now it’s improving the Furin cleavage site even further:

Note that all three of these amino acids it tries out here require double nucleotide mutations. A double nucleotide mutation is pretty rare in itself, so to see it do this three times at the same position, arriving at three different amino acids, suggests it’s under very big pressure to change this position.

Out of these three, the most logical one based off what I’ve so far explained to you would be the Arginine one at the bottom. But time will tell. All three probably carry some benefit.

So as you’ll notice, none of these mutations to the Furin cleavage site have ever been seen before, until BA.2.86. So why is this happening now?

Well, the whole population has antibodies against the Spike protein now. Any virus that wants to infect us, needs to figure out how to deal with those antibodies. When everyone has similar antibodies against a few positions, the easy way to escape those antibodies is by mutating those positions. But eventually, the whole population will have different antibodies against different parts of the Spike protein, due to differing waves of infection. That makes that strategy difficult.

So what happens then? Well, the other way of antibody escape that can work is increasing ACE2 affinity. Bind to the proper receptor, before antibodies get a chance to bind. This is a strategy that works more easily, when antibody concentrations decline.

So when the vanishing act started a few months ago, I warned you the virus would just return more fiercely than before. And it did. A new version managed to establish a foothold in the population once antibody concentrations began to decline this summer, that has the higher ACE2 affinity you would expect, higher than any version of the virus ever seen.

So I think the most likely explanation for why this is now happening, is that the BA.2.86 variant can afford to sacrifice some ACE2 affinity to improve its Furin cleavage site.

We learned from Delta that an improvement to the Furin site increases the virulence. Now that we see further improvements to the Furin cleavage site, I expect we will also see further increases in virulence.

Maybe some of you will arrive at very different conclusions (I’d be happy to hear the arguments), but it looks to me like the Omicron lull is about to come to a dramatic end. As I’ve said before, historically it took generations for corona virus outbreaks in our ancestors to unleash their full potential.


  1. My view, the acute infection is not the main issue. The prionogenic peptides that are left behind, on each reinfection, are the bigger problem, in my opinion.

    • Yeah I agree, the long term impact seems worse than the acute infection. The virus is neurovirulent, it draws T cells into the brain, there’s acute increases of amyloid worse than in Alzheimer’s patients, prionogenic peptides, long lasting brain inflammation, neurons that fuse together and other misery.

      Influenza doesn’t do this. You don’t see T cells enter the brain after an influenza infection.

      We see this stuff in all the other animals they test this virus on too. Dogs, primates, mice, they all show brain damage from this virus. But unlike a dog, whose brain needs to last fifteen years, our brain needs to last ninety years.

      I think it’s contributing to the insane behavior we see all around us. Everyone’s slowly going mad.

  2. I’m still of two minds regarding nasal rinsing with antiseptic saltwater solution as prophylaxis. This is being advocated by people like Harvard2TheBigHouse (he is an even bigger COVID doomsayer than Dr. Geert Vanden Bossche, as if that was even possible). On the one hand, this should theoretically prevent you from becoming infected with these nasty neurovirulant strains. However, this lack of training of your immune system could be setting you up for a bigger failure down the road once you inevitably do become infected with a future strain. Then, you could end up being a “sitting duck” with a naive immune system, just like the Native Americans were when the European colonizers introduced a plethora of diseases when they arrived in the New World.

    • Yes, I’ve been wondering about that trade off for a long time now. I still haven’t caught covid; one reason is that I use Xlear nasal spray. But maybe I had an asymptomatic case at some point? That wasn’t picked up by my still-required-by-volunteer-position weekly RAT test (required since I’m not vaxxed)? So maybe I have no antibodies. But I don’t want to infect my obese husband or my ancient father in law or my innocent dogs, so I’m still avoiding it. Also the prospect of dropping from midwit to lowwit is really unappealing.

      I noticed the strangest thing recently. I have plenty of life experiences of small accidental cuts (including puppy bites) and how they heal. They’ve always bled a bit, and I’ve needed a bandaid. But we’ve now had puppies for a month and the puppy fang cuts are not acting that way. They clot instantly; I can see the blood clot!!! I can see it firm up as I watch!!! No bandaid needed. It is creepy. And I take natto-serra. WTF.

      Everyone at Trader Joe’s looks sick. It is especially horribly evident with young Asian women, since they have always in the past looked perfect, and they normally age really well. Now they all have slightly greyish skin and the sort of hollows under their eyes that most white women get in late middle age on but Asian women don’t until they are very old. And the white women I see have the eye hollows in their 30s now. It has to do with tendons and covid does affect tendons. This is Silicon Valley and almost everyone is multi vaccinated so I don’t know if it is covid or the shot.

      • Maybe it’s synergy. Repeated low-level reinfections on top of the vaccines. I see a few people at a coffeehouse I frequent that look the way you describe.

  3. Doesn’t natto make your blood clot better? I eat natto daily and had my wisdom teeth remover, no blood at al, fastest healing ever, dentist was really impressed.
    I do believe in the power of natto

    • I’m not sure. I haven’t delved into this, but I suspect the body pursues homeostasis. If you introduce exogenous fibrinolytic capacity, it may reduce its own production.

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The patients in the mental ward have had their daily dose of xanax and calmed down it seems, so most of your comments should be automatically posted again. Try not to annoy me with your low IQ low status white male theories about the Nazi gas chambers being fake or CO2 being harmless plant food and we can all get along. Have fun!

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