> This furin-like cleavage site...may provide a gain-of-function to the 2019-nCoV for efficient spreading in the human population compared to other lineage b beta- coronaviruses.
Can somebody who understands this please elaborate on the implications?
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.)
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.
> ...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
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 :
I’m thinking what the heck is a Gainof Function?
For a virus I suppose this would be function in reproduction.
[1] https://journals.sagepub.com/doi/abs/10.1177/030631271666642...