Chat message

Slack / Private Message Drop, pp.58-59 [SLACK_000272] · slack_pm:msg:00589

Date: 2020-06-06 09:21
Type: chat message · slack
recipient: Robert F. Garry, Edward C. Holmes, Andrew Rambaut
speaker: Kristian G. Andersen
Topics: Furin cleavage site and molecular features Intelligence community assessments

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The eLife and flu 'polymerase slippage' papers are very interesting indeed. As to how beneficial the furin site is inhumans, I thought this one was reasonably interesting (although I don't believe we have seen this in our sequences- we'll dig deeper):https://www.biorxiv.org/content/10.1101/2020.06.03.129585v1Between the flu and eLife papers, how about a hypothesis where the virus might have been introduced into (denselypacked) farmed animals and then maybe bouncing back and forth between the animals and humans for a (little) while. That'd explain the lack of positive selection in the spike (which really is *highly* unusual IMO) and also the acquisition of the furin site - it clearly seems like some sort of heavy passaging must have been required to gain that site. Checking ENaC and SARS-2, while the AAs are indeed conserved, the nucleotides are not - specifically ENaC isusing human high-frequency codons, whereas SARS-2 is not. Need to check out loop structures around the furin site in SARS-1, as well as in a putative SARS-2 without the furin site. How close are we to the scenario described in the flu paper?

Links shared

preprint https://www.biorxiv.org/content/10.1101/2020.06.03.129585v1Between

Extracted statements

Rule-extracted, not adjudicated. The grade says what may be done with each one; read the document above before relying on any of them.

Statement	Grade	Attribution	Stance
As to how beneficial the furin site is inhumans, I thought this one was reasonably interesting (although I don't believe we have seen this in our sequences- we'll dig deeper):https://www.biorxiv.org/content/10.1101/2020.06.03.129585v1Between the flu and eLife papers, how about a hypothesis where the virus might have been introduced into (denselypacked) farmed animals and then maybe bouncing back and forth between the animals and humans for a (little) while.	quoted / not their view	draft_language proposed document wording	asserts
That'd explain the lack of positive selection in the spike (which really is highly unusual IMO) and also the acquisition of the furin site - it clearly seems like some sort of heavy passaging must have been required to gain that site.	needs context	uncertain explicit hedge	asserts

Statement

Grade

Attribution

Stance

As to how beneficial the furin site is inhumans, I thought this one was reasonably interesting (although I don't believe we have seen this in our sequences- we'll dig deeper):https://www.biorxiv.org/content/10.1101/2020.06.03.129585v1Between the flu and eLife papers, how about a hypothesis where the virus might have been introduced into (denselypacked) farmed animals and then maybe bouncing back and forth between the animals and humans for a (little) while.

quoted / not their view

draft_language proposed document wording

asserts

That'd explain the lack of positive selection in the spike (which really is *highly* unusual IMO) and also the acquisition of the furin site - it clearly seems like some sort of heavy passaging must have been required to gain that site.

needs context

uncertain explicit hedge

asserts

In context

A single line often inverts meaning once you see what it answers, so neighbouring messages are always shown.

2020-06-06 09:21 Kristian G. Andersen

The eLife and flu 'polymerase slippage' papers are very interesting indeed. As to how beneficial the furin site is inhumans, I thought this one was reasonably interesting (although I don't believe we have seen this in our sequences- we'll dig deeper):https://www.biorxiv.org/content/10.1101/2020.06.03.129585v1Between the flu and eLife papers, how about a hypothesis where the virus might have been introduced into (denselypacked) farmed animals and then maybe bouncing back and forth between the animals and humans for a (little) while. That'd explain the lack of positive selection in the spike (which really is *highly* unusual IMO) and also the acquisition of the furin site - it clearly seems like some sort of heavy passaging must have been required to gain that site. Checking ENaC and SARS-2, while the AAs are indeed conserved, the nucleotides are not - specifically ENaC isusing human high-frequency codons, whereas SARS-2 is not. Need to check out loop structures around the furin site in SARS-1, as well as in a putative SARS-2 without the furin site. How close are we to the scenario described in the flu paper?
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]
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.
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)
2020-06-06 10:20 Andrew Rambaut open

Farm sounds good to me.

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