4 ms·

Edit: found this below https://news.ycombinator.com/item?id=22535930 https://news.ycombinator.com/item?id=22535930 (see sampo’s response in comments) I am comp

Edit: found this below https://news.ycombinator.com/item?id=22535930 https://news.ycombinator.com/item?id=22535930 (see sampo’s response in comments) I am completely baffled to the meaning of this given the scientific nomenclature used, but I would really like to know what it means and why it is front page HN. What I imagine it means is that the red things on this picture https://www.cdc.gov/homepage/images/banner/covid-19-1330px.jpg https://www.cdc.gov/homepage/images/banner/covid-19-1330px.j... have some sort of indentation, or cleavage, that makes them either more or less dangerous. Am I close? Can someone who understands explain for the layman?

jforman 7y ago
tl;dr any unique feature of this virus may be explanatory for its demonstrably increased virulence, and may be targetable by existing therapeutics as well. This particular feature is a candidate finding of this type — the specific molecular biology involved isn't particularly important for non-molecular biologists (I was one in a past life).
conspiracyjoe 7y ago
No idea. Only other context I've come across this as a lay person is in describing gain of function research. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4996883/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4996883/ Not sure that's what the other intended though, would appreciate someone with technical understanding interpreting.
zimpenfish 7y ago
Yeah, I think it's the "peculiar furin-like cleavage site in the Spike protein" that's the new mutation which might make this variant more efficient in spreading. As best I can tell as a biological layman.
- rolph 7y ago
  yes you have it this is the concept.
unchocked 7y ago
Gain of function describes a mutation in COVID-19 that causes it to do something new. This is different from most mutations, which are loss of function, causing it to stop doing something old. The gain of function mutation is a cleavage site, which means that a new protein can be created, which could have some new activity. This cleavage site looks like a Furin cleavage site: Furin is associated with transporting proteins inside a cell, and thus with infection. So a drug targeting the Furin pathway may block the effect of this gain of function mutation, and make COVID-19 less infections to those taking it.
wjn0 7y ago
Gain-of-function literally only means the protein has, in some sense, gotten better at its "job" (or has taken on an additional "job"). In this case, the "job" of the protein is to infect organisms more effectively. Some background: viruses primarily contain the genetic material and a protein coat. The Spike (S) protein is one of the proteins in the coat, and plays a role in whether an infection will take root. From the paper: > we identified a peculiar furin-like cleavage site in the Spike protein of the 2019-nCoV, lacking in the other SARS-like CoVs Furin is a protease that is present in healthy humans. Some proteins aren't "active" until they're cut (cleaved) at specific sites along their sequence, so furin's "job" is to cleave these proteins - activating them. Notably, furin is highly expressed in the lungs. 2019-nCoV apparently has a "furin-like site" in its Spike protein - a sequence that furin can bind to and cleave. Notably, furin is the protease that cleaves one of the proteins in the protein coat of HIV, which then allows for viral replication [1]. The authors therefore hypothesize that this mutation which creates the furin-like cleavage site accounts for some of the pathogenicity of 2019-nCoV. They further hypothesize that furin inhibitors may be effective agents in combating the virus (which have shown some promise in combating other viruses, tumours, etc.). Disclaimer: not a virologist, just a computational biologist with a bit of interest in structural biology. Also, the authors emphasize that further experimentation needs to be done to validate this claim. [1] doi:10.1038/360358a0
vikramkr 7y ago
I think sampo gave a concise explanation- I tried to clarify the terminology and mechanics around gain of function-loss of function in my comment below (since I think function means different thing to different people) - basically, there's potentially a mutation in those spike proteins that makes the virus more infective if it turns out to be supported by lab experiements, gain of function just means that the mutation makes the protein work better or gives it a new functionality instead of breaking it.
rolph 7y ago
yes you have the concept.

jforman 7y ago

tl;dr any unique feature of this virus may be explanatory for its demonstrably increased virulence, and may be targetable by existing therapeutics as well. This particular feature is a candidate finding of this type — the specific molecular biology involved isn't particularly important for non-molecular biologists (I was one in a past life).

conspiracyjoe 7y ago

No idea. Only other context I've come across this as a lay person is in describing gain of function research. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4996883/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4996883/ Not sure that's what the other intended though, would appreciate someone with technical understanding interpreting.

zimpenfish 7y ago

Yeah, I think it's the "peculiar furin-like cleavage site in the Spike protein" that's the new mutation which might make this variant more efficient in spreading. As best I can tell as a biological layman.

rolph 7y ago
yes you have it this is the concept.

unchocked 7y ago

Gain of function describes a mutation in COVID-19 that causes it to do something new. This is different from most mutations, which are loss of function, causing it to stop doing something old. The gain of function mutation is a cleavage site, which means that a new protein can be created, which could have some new activity. This cleavage site looks like a Furin cleavage site: Furin is associated with transporting proteins inside a cell, and thus with infection. So a drug targeting the Furin pathway may block the effect of this gain of function mutation, and make COVID-19 less infections to those taking it.

wjn0 7y ago

Gain-of-function literally only means the protein has, in some sense, gotten better at its "job" (or has taken on an additional "job"). In this case, the "job" of the protein is to infect organisms more effectively. Some background: viruses primarily contain the genetic material and a protein coat. The Spike (S) protein is one of the proteins in the coat, and plays a role in whether an infection will take root. From the paper: > we identified a peculiar furin-like cleavage site in the Spike protein of the 2019-nCoV, lacking in the other SARS-like CoVs Furin is a protease that is present in healthy humans. Some proteins aren't "active" until they're cut (cleaved) at specific sites along their sequence, so furin's "job" is to cleave these proteins - activating them. Notably, furin is highly expressed in the lungs. 2019-nCoV apparently has a "furin-like site" in its Spike protein - a sequence that furin can bind to and cleave. Notably, furin is the protease that cleaves one of the proteins in the protein coat of HIV, which then allows for viral replication [1]. The authors therefore hypothesize that this mutation which creates the furin-like cleavage site accounts for some of the pathogenicity of 2019-nCoV. They further hypothesize that furin inhibitors may be effective agents in combating the virus (which have shown some promise in combating other viruses, tumours, etc.). Disclaimer: not a virologist, just a computational biologist with a bit of interest in structural biology. Also, the authors emphasize that further experimentation needs to be done to validate this claim. [1] doi:10.1038/360358a0

vikramkr 7y ago

I think sampo gave a concise explanation- I tried to clarify the terminology and mechanics around gain of function-loss of function in my comment below (since I think function means different thing to different people) - basically, there's potentially a mutation in those spike proteins that makes the virus more infective if it turns out to be supported by lab experiements, gain of function just means that the mutation makes the protein work better or gives it a new functionality instead of breaking it.

rolph 7y ago

yes you have the concept.