Slack / Private Message Drop — page 72

risks and don't seem to think that a natural explanation is more likely than lab culture. [2020-06-11 17:01:47] [Eddie Holmes] Fair points. But that work isn't exclusively done at the WIV because as you say yourself the Baric lab are doing it. I still don't quite see what the new data is. The bovine stuff? What else is there? To me, there is more evidence against lab escape than when we wrote the paper. I think the bats not roosting in winter argument is nothing because I reckon it went through an intermediate host anyway. Do you have a copy of the EgoHealth grant? [2020-06-11 17:07:00] [Kristian Andersen] Aim3: https://projectreporter.nih.gov/project_info_description.cfm?aid=9819304&icde=50404048&ddpara m=&ddvalue=&ddsub=&cr=1&csb=FY&cs=DESC&pball= [2020-06-11 17:11:58] [Kristian Andersen] > But that work isn't exclusively done at the WIV because as you say yourself the Baric lab are doing it No, that work _is_ exclusively at WIV AFAIK. Baric's lab is doing (did) gain of function research where they created reverse genetics systems to study the viruses. All of this is done in BSL-3, so much (much!) less risk of exposure. The work in Shi's lab is different - here they are taking bat CoVs and culturing them under BSL-2 in cell lines from different animals - to e.g., understand which ones can infect human cells and what type of mutations that occur in T/C may make them permissive. They probably have more than 10 papers where they describe that type of work on all kinds of SARS-like CoVs. [2020-06-11 17:14:11] [Eddie Holmes] Got it, thanks. That helps. [2020-06-11 17:16:59] [Eddie Holmes] Have the Shi lab published all the viruses they use in these culture experiments? Do they find the same mutations that appear in SARS-CoV-2? [2020-06-11 17:21:19] [Kristian Andersen] In our paper we argue against (a) manipulation and (b) tissue culture. Our main arguments were that manipulation is hard, but the German's came out and created a reverse genetics system of SARS2 in less than two weeks, so clearly it's not that hard. Our arguments against tissue culture mostly came down to the O-linked glycans and a 'mucin-like' domain. But by now it seems clear that these don't actually form a mucin-like domain, but rather those glycans modulate the function of the furin site. All our arguments about natural viruses emerging, the RBD identical in pangolin CoVs, etc., all still stand. The main new things that bothers me the most: 1. Lack of selection (a lot of the selection is for replication in a particular host species, so yes, I would assume culture would lover selection during subsequent transmission in humans - however, immune selection will still occur). 2. Gain of furin cleavage of bovine CoV in tissue culture. 3. Loss of furin site in tissue culture meaning it's active. 4. The little details about the furin site - e.g., that it's exactly in the spot where experiments had previously inserted it, the fact that the exact sequence exist in a cat CoV, Shi herself being sketchy with details and considering lab accident, etc. But all of this can go both ways [2020-06-11 17:21:58] [Kristian Andersen] Unclear to me if they published sequences of all these viruses - it's a lot and names are changing over time (e.g., RaTG13 had a different name previously). [2020-06-11 17:23:02]