A hell of a lot of what they say about furin is simply wrong. Insertions and deletions happen ALL THE TIME in nature and while rarer than SNPs are not uncommon, around the cleavage site loop there are other indels in related viruses, the furin site is DECIDEDLY suboptimal for cleavage such that all the fun lineages that are more contagious are optimizing it and creating actual canonical sites rather than something just good enough, it is generated out of frame in in a way that no sane biologist ever would, and the glycosylation pattern nearby weakly suggests it appeared in the context of an actual immune system rather than cell culture.
The alignments they point to arguing for other differences in the cleavage sites in other viruses being due to SNPs rather than insertions are laughable, and from people who I have found to have a poor grasp of the underlying science.
On top of all that when conditioning on something that successfully changes species you will enrich for things that broaden their tropism, which that kind of cleavage site will do, so of course things that are rarer but helpful will pop up more than if you were looking at the space of all possible mutations without conditioning.
A hell of a lot of what they say about furin is simply wrong. Insertions and deletions happen ALL THE TIME in nature and while rarer than SNPs are not uncommon, around the cleavage site loop there are other indels in related viruses, the furin site is DECIDEDLY suboptimal for cleavage such that all the fun lineages that are more contagious are optimizing it and creating actual canonical sites rather than something just good enough, it is generated out of frame in in a way that no sane biologist ever would, and the glycosylation pattern nearby weakly suggests it appeared in the context of an actual immune system rather than cell culture.
The alignments they point to arguing for other differences in the cleavage sites in other viruses being due to SNPs rather than insertions are laughable, and from people who I have found to have a poor grasp of the underlying science.
On top of all that when conditioning on something that successfully changes species you will enrich for things that broaden their tropism, which that kind of cleavage site will do, so of course things that are rarer but helpful will pop up more than if you were looking at the space of all possible mutations without conditioning.