3 ms·

It isn't unusual at all. Many coronaviruses including MERS have a furin cleavage site and they're common and likely evolved independently multiple times, showi

It isn't unusual at all. Many coronaviruses including MERS have a furin cleavage site and they're common and likely evolved independently multiple times, showing that this acquisition of an FCS is common: https://www.sciencedirect.com/science/article/pii/S1873506120304165 https://www.sciencedirect.com/science/article/pii/S187350612... The FCS in SARS-CoV-2 is NSPRRAR, we now know of sarbecoviruses like like the BANAL viruses in Laos which have NSPAAR, some other viruses like RmYN02 have NSPAAR or NSPVAR. If you insert an R into the BANAL spike protein you get the SARS-CoV-2 FCS. https://www.nature.com/articles/d41586-021-02596-2 https://www.nature.com/articles/d41586-021-02596-2 https://www.biorxiv.org/content/10.1101/2021.01.26.428212v1 https://www.biorxiv.org/content/10.1101/2021.01.26.428212v1 Finding bat sarbecoviruses which are one insertion away from having the original FCS really blows a gaping hole in this whole idea that the FCS is some kind of smoking gun. Delta has P681R and Omicron has P681H mutations in the FCS region which may be behind why they're more infectious/transmissible. So the FCS is also still evolving and adapting to humans.

tim333 5y ago
You're answering why furin cleavage sites in general are not unusual. Not why this particular furin cleavage site is unusual from a natural evolutionary view. It's if you line up the related bat coronaviruses sequences they are all much the same in that region apart from Sars-Cov-2 which seems to have a clean insert of a PRRA sequence. Hence the "bothered by the furin site and has a hard time (to) explain that as an event outside the lab, though there are possible ways in nature but highly unlikely." in the article. If it had got there through evolution you'd expect the adjacent sequences to vary more. This kind of thing https://media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10311-021-01211-0/MediaObjects/10311_2021_1211_Fig3_HTML.png?as=webp https://media.springernature.com/lw685/springer-static/image...
- lamontcg 5y ago
  Here is that kind of thing: https://ibb.co/T1YtShy https://ibb.co/T1YtShy That is from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211627/#mmc1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211627/#mmc1 Specifically the lower bit of figure 2: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211627/figure/fig2/?report=objectonly https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211627/figure/... If RmYN02 picks up the QTQT sequence from recombination with other bat coronaviruses (or RmYN02 is a deletion away from a common progenitor we haven't found yet -- and the QTQT deletion is seen in SARS-CoV-2 variants in humans) then it is one insertion away from PRAAR which would be an active FCS, which is then one substitution away from the PRRAR SARS-CoV-2.

tim333 5y ago

You're answering why furin cleavage sites in general are not unusual. Not why this particular furin cleavage site is unusual from a natural evolutionary view. It's if you line up the related bat coronaviruses sequences they are all much the same in that region apart from Sars-Cov-2 which seems to have a clean insert of a PRRA sequence. Hence the "bothered by the furin site and has a hard time (to) explain that as an event outside the lab, though there are possible ways in nature but highly unlikely." in the article. If it had got there through evolution you'd expect the adjacent sequences to vary more. This kind of thing https://media.springernature.com/lw685/springer-static/image/art%3A10.1007%2Fs10311-021-01211-0/MediaObjects/10311_2021_1211_Fig3_HTML.png?as=webp https://media.springernature.com/lw685/springer-static/image...

lamontcg 5y ago
Here is that kind of thing: https://ibb.co/T1YtShy https://ibb.co/T1YtShy That is from: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211627/#mmc1 https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211627/#mmc1 Specifically the lower bit of figure 2: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211627/figure/fig2/?report=objectonly https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7211627/figure/... If RmYN02 picks up the QTQT sequence from recombination with other bat coronaviruses (or RmYN02 is a deletion away from a common progenitor we haven't found yet -- and the QTQT deletion is seen in SARS-CoV-2 variants in humans) then it is one insertion away from PRAAR which would be an active FCS, which is then one substitution away from the PRRAR SARS-CoV-2.