Some proteins are inactive first after they have been synthesized. Furin is an enzyme that targets certain sites in certain biomolecules and cuts a piece off, activating these proteins. Apparently some furin is floating around in the human body for this purpose. The article suggest that there is a furin target site (binding site) in the surface "spikes" of the coronavirus. And when furin cuts piece off the spikes, the resulting, or remaining, part then assists the entry of the virus into cells.

Here is a review article from 2019 on furin. Apparently several viruses use this "trick" as part of their entry mechanism.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6682551/

(I have some biology studies from long ago, I am not professional in molecular biology.)

They talk about a "cleavage site", meaning a 3D shape with the chemical properties necessary to cut something. And apparently, that ability to cut molecules similar to furin enables this virus to more efficiently enter cells, i.e. successfully infecting someone with a lower dose of live viruses.

Where this new shape came from, they do not know. But since viruses tend to mutate a lot and integrate RNA snippets floating around in their host's blood stream, it is likely that they picked it up from some other virus simultaneously infecting the same individual.

In short, the new nCoV seems to be so contagious because it merged in a new feature from a different virus species.

The implication is that by specifically blocking this thing that nCov has but older Cov do not have, one might be able to drastically reduce its contagiousness.

The analysis they present doesn't require the integration of foreign RNA. 2019nCov has a SPRR motif, where other viruses has similar motifs (SRRK, KNRR, TPRS...). It can be explained with mutations, and in fact they talk about convergent evolution.

Small elaboration: it didn’t “merge in” this feature, it independently evolved it (“convergent evolutionary pathway”), which implies it’s a particularly handy feature for this virus to have. (For the virus, not so much for us.)

The cleavage site is the target that gets cleaved, not the part that does the cutting. So in this case the virus has a site that can be cleaved by certain enzymes like Furin.

Indeed: https://en.wikipedia.org/wiki/Furin

From the Wiki page for Furin

> ...must be cleaved by furin or furin-like proteases to become fully functional. Anthrax toxin, pseudomonas exotoxin, and papillomaviruses must be processed by furin during their initial entry into host cells.

From the sound of this:

- the site on the virus gets cleaved - Furin enables the cleaving - Furin exists in hosts cells

What I think I understand is, the cleaving makes it easier for the virus to reproduce inside the cell?

edit: turns out I have no idea how to format things on HN

the cleaving prepares the virus to be able to enter the cell

there is a protien on the virus that is called S [spike].

there is a protien [protease] in the extracellular space of your tissues that cleaves other protiens these are called Furins.

Furins activate enzymes where they are needed by cleaving [cutting away all the shipping wrap].

The S protien of the nCoV SARS 2 virus has a cleavage site that is cut by the furin class of protiens.

this seems to be a modification as the SARS CoV does not have this cleavage site as far as can be seen for the time.

so what does this do?

the S protien is specific to a binding site [ACE2] and that will be found in high prevalence in the lungs, but is found elsewhere. the corona virus does not seem to shed through the skin but through mucous and sputum so the virus that is efficient at lung infection will win when this is its transmission mode.

if the virus doesnt make it to the lungs it is in a less than optimal place for survival compared to the lungs.

so the virus has a specific tag recognition sequence to find ACE2 and stick.

this is where the Furin comes in. The S protien is in shipping state until it reaches the lungs and is cleaved by Furin, this is when the S protien become S1; S2.

the S1 stays bound to ACE2, the S2 does some work and wrenches the cell membrane open then inserts its nucleocapsid---this is now an infection.

the exact details are not entirely worked out such as is there an absolute requirement for S binding or S cleavage in any particular order. and does anything else participate in the process.

the authour suggests some correlation of furin cleavage sites with increased pathogenicity [potential to cause disease] based on observations of other unrelated virus having a newly acquired cleavage site correlated with increased proclivity to cause a disease process in humans.

there may be some undercurrent regarding these molecular feature as a general theme in biology, however there is not a firm scientific consensus that this is the case.

the articel referenced is a preproof meaning it is close to being accepted for publishing so it isnt science yet.

[PDF] here :

https://sci-hub.se/10.1016/j.antiviral.2020.104742

The phrase "gain of function" seems to mean the virus differs in some way that makes it more contagious or deadly.

Yes, and here is a good overview of it in the context of some contentious research [1].

[1] https://journals.sagepub.com/doi/abs/10.1177/030631271666642...

Seems interesting, but I can't read that without paying, and I probably lack the background necessary for it to be understandable.

Type the DOI into sci-hub.tw

Thanks. Didn't know this existed.

you can copy it like a link as well and paste it in

Thank you, that makes a lot more sense than some sort of “gain” (as in, increasing output levels) of “function” (as in, a mathematical calculation where each input has exactly one output).

I’m thinking what the heck is a Gainof Function?

Yeah the function here is not a mathematical function - it just means functionality, like the thing that it can do. Sometimes we biologists can be spectacularly uncreative in naming things :)

Heh, It makes more sense if you think about it medically. Like, the gain or loss of function in a limb or organ.

For a virus I suppose this would be function in reproduction.

It does not mean that.

Their previous comment

> Humans are notoriously good at coming up with bullshit explanations for both random/statistical & deterministic phenomena.

Apt.

This has been a debunked conspiracy theory.