Chat message

Slack / Private Message Drop, p.149 [SLACK_000363] · slack_pm:msg:01529

Date: 2020-08-29 15:33
Type: chat message · slack
recipient: Kristian G. Andersen, Robert F. Garry, Andrew Rambaut
speaker: Edward C. Holmes
Topics: Intelligence community assessments Furin cleavage site and molecular features

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We await the paper, but the key point is that (they claim) these were SARS-CoV related. To me, this makes perfect sense: obviously, prior to the pandemic they would have been most interested in viruses related to the known human pathogen (SARS-CoV) rather than to random bat viruses in a completely different part of the tree. That said, the Embevoviruses (e.g. HKU-1) more often have furin sites and seem to be more often rodent associated. Does make you think about rodent hosts.

Extracted statements

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Statement	Grade	Attribution	Stance
HKU-1) more often have furin sites and seem to be more often rodent associated.	quoted / not their view	quoted_external attribution frame: 'That said,'	asserts

Statement

Grade

Attribution

Stance

HKU-1) more often have furin sites and seem to be more often rodent associated.

quoted / not their view

quoted_external attribution frame: 'That said,'

asserts

In context

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

2020-08-29 15:33 Edward C. Holmes

We await the paper, but the key point is that (they claim) these were SARS-CoV related. To me, this makes perfect sense: obviously, prior to the pandemic they would have been most interested in viruses related to the known human pathogen (SARS-CoV) rather than to random bat viruses in a completely different part of the tree. That said, the Embevoviruses (e.g. HKU-1) more often have furin sites and seem to be more often rodent associated. Does make you think about rodent hosts.
2020-08-29 15:41 Kristian G. Andersen open

To me the main interest is that they have a rodent model where SARS-CoV-2 can grow very rapidly. Previously we have talked about "passage in animals" and concluded that that type of work would have required e.g., ferrets, which would have been a lot harder. But having a mouse colony with human ACE2s make large-scale culturing experiments with something like SARS-CoV-2 easy. But yeah, this type of work was all part of the EgoHealth grant, so no surprises that they had the models. But on the question of "could they have performed large-scale culturing models in animals", where we had previously leaned"very unlikely" that's now "very likely" - having this type of mouse available makes a big difference. Doesn't change anything, but need to keep this in mind.
2020-08-29 15:45 Edward C. Holmes open

True, but I don't see how a passage in a mouse model would produce a virus so well adapted to humans and with that RBD. Makes no sense to me at all. I'm leaning more toward the idea that it was circulating in humans for a while but was undetected....one lineage then exploded in Wuhan.
2020-08-29 15:53 Kristian G. Andersen open

That's the key here - that mouse model is using the human ACE2 receptor, so it'd be a perfect fit - plus the acquisition of furin sites during rapid passage as we discussed in the paper (as is seen for flu). Can't be dismissed out of hand as what she's saying in her answer that they were doing exactly those types of experiments. Doing that type of work with a novel (bat) CoV would constitute a non-trivial risk for sure - she does not mention whether this isBSL-2 or BSL-3, but likely the former. But I'm glad you're now leaning towards the "pre-circulation" theory - now we just need to have Andrew come around to that :wink:
2020-08-29 16:02 Edward C. Holmes open

Fair point about ACE2, but the RBD is very different to SARS-CoV. To me, if the furin cleavage site is active in cell culture then it is also likely to be active in evolution. This also means that she and and a lot of people of lying. Why admit to this stuff in interview if something dodgy had happened? Also, there is absolutely NO intelligence and NOchatter about them doing these experiments. People talk about their work and there would be no reason to cover itup then.

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