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Slack / Private Message Drop, p.59 [SLACK_000273] · slack_pm:msg:00594

Page text: p.59 · original PDF

Date
2020-06-06 10:35
Type
chat message · slack
recipient
Robert F. Garry, Edward C. Holmes, Andrew Rambaut
speaker
Kristian G. Andersen
Topics
Furin cleavage site and molecular featuresIntelligence community assessments

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Actually, this just occurred to me and I'm wondering if the UK dataset could help investigate. Is it possible that the furin site is advantageous during high passage scenarios (transmission) but maybe not so much within host? In that scenario, maybe the furin cleavage site is maintained during exponentially increasing outbreaks (like we have observed up until about a month ago), but might be lost during more low-transmission periods? (as is the case insome places currently).In the bioRxiv paper above, they observe loss of the site in a subset of patients, but only intra-host, so based onthat, it might be possible that the site _can_ be lost in human infections too, and not just in tissue culture. To see ifthere's a link to transmissions, if we look at viruses sequenced in low-transmission places (or during low-transmission times) vs viruses sequenced in high-transmission places (or times), is there an association with the former showing more evidence of furin site loss than the latter? Would be pretty cool if that was the case...

Extracted statements

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StatementGradeAttributionStance
Is it possible that the furin site is advantageous during high passage scenarios (transmission) but maybe not so much within host? needs context uncertain explicit hedge questions
In that scenario, maybe the furin cleavage site is maintained during exponentially increasing outbreaks (like we have observed up until about a month ago), but might be lost during more low-transmission periods? needs context uncertain explicit hedge questions
To see ifthere's a link to transmissions, if we look at viruses sequenced in low-transmission places (or during low-transmission times) vs viruses sequenced in high-transmission places (or times), is there an association with the former showing more evidence of furin site loss than the latter? needs context speaker_own questions

In context

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  1. 2020-06-06 09:22 Kristian G. Andersen open
    Here's the alignment of furin site ENaC and SARS-2 [shared file(s): Screen Shot 2020-06-06 at 8.58.49 AM.png]
  2. 2020-06-06 09:49 Andrew Rambaut open
    So only one codon the same. I got to say - Bill's HKU9 source still seems good to me. But perhaps it did happen in amink/ferret/pangolin/civet/cat/etc.
  3. 2020-06-06 10:14 Kristian G. Andersen open
    Yeah, I think Bill's explanation is basically the "hairpin followed by polymerase slippage in flu" CoV equivalent. Issueis - it could have happened anywhere.... I'm thinking a theory involving a farm isn't completely crazy - I believe Drosten is leaning that way too (and thought maybe even SARS1 could have started that way)
  4. 2020-06-06 10:20 Andrew Rambaut open
    Farm sounds good to me.
  5. 2020-06-06 10:35 Kristian G. Andersen
    Actually, this just occurred to me and I'm wondering if the UK dataset could help investigate. Is it possible that the furin site is advantageous during high passage scenarios (transmission) but maybe not so much within host? In that scenario, maybe the furin cleavage site is maintained during exponentially increasing outbreaks (like we have observed up until about a month ago), but might be lost during more low-transmission periods? (as is the case insome places currently).In the bioRxiv paper above, they observe loss of the site in a subset of patients, but only intra-host, so based onthat, it might be possible that the site _can_ be lost in human infections too, and not just in tissue culture. To see ifthere's a link to transmissions, if we look at viruses sequenced in low-transmission places (or during low-transmission times) vs viruses sequenced in high-transmission places (or times), is there an association with the former showing more evidence of furin site loss than the latter? Would be pretty cool if that was the case...

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