Natural origin / zoonotic spillover

```We also demonstrate that SARS-CoV-2's entire RBM was introduced through recombination with coronaviruses from pangolins``` Nope.

Slack / Private Message Drop, p.46 · original PDF · in context

Strictly confidentially, I literally (2 mins ago) just got an email that says: "Recently, we isolated a pangolin-Cov that ishighly related with SARS-CoV-2 (https://www.nature.com/articles/s41586-020-2313-x).

Slack / Private Message Drop, p.73 · original PDF · in context

No one gives a shit and now we are seeing loads of pangolins with frothy lungs.

Slack / Private Message Drop, p.74 · original PDF · in context

That Viruses paper on the pangolin virus, which does not even describe the sequence, was published online in Oct. 24th 2019.

Slack / Private Message Drop, p.76 · original PDF · in context

It's obviously not credible tohave read this, got the pangolins and the viruses and done the leaky experiments in this timeline; (ii) the WIV is not the only lab with closely related bat viruses - obviously RmYN02 comes from a different lab; (iii) I don't see that 4amino acid insertion and no flanking changes is at all problematic, particularly as these insertions are so commone.g. in H7N7 AIV the sequence went from PEIPKGR (low path) to PEIP*KRRR*R (high path).

Slack / Private Message Drop, p.76 · original PDF · in context

I have talked to a few journalists about the origins recently but only if they seem genuinely interestedin the natural origins.

Slack / Private Message Drop, p.77 · original PDF · in context

Large variety of pangolin viruses (these are illegally imported from SE Asia - so where are they getting them from).

Slack / Private Message Drop, p.77 · original PDF · in context

Shows better how the pangolin distance is exactly the same in the variable as the rest of the CTD whereas RaTG13jumps out.

Slack / Private Message Drop, p.78 · original PDF · in context

Alas, the involvement of WHO will upset some people but Idon't know what else is feasible; (iii) to me, the pangolin story is crucial: the RBD looked 'anomalous' but then a littleof sampling of an animal what we would never have expected found it was there in nature; (iv) yes, there are some new data points but it is also very clear that we really need better sample of nature to sort this out.

Slack / Private Message Drop, p.78 · original PDF · in context

Doubtless there will be more bat viruses out there that fill in key positions, but if random animals like pangolins are in the mix (and these were smuggled into China from elsewhere) only god or George Gao knows what else is out there.

Slack / Private Message Drop, p.78 · original PDF · in context

Just talked to David Quammen who is writing a piece for the New Yorker about pangolin conservation (with some CoV angles).

Slack / Private Message Drop, p.79 · original PDF · in context

The two pangolin papers in Nature (different groups) both show the same RBD in the animals from Guangdong.

Slack / Private Message Drop, p.85 · original PDF · in context

But the pangolin sequence is only 'highly identical' at the amino acid level.

Slack / Private Message Drop, p.85 · original PDF · in context

The similarity between the RBD and the Guangdong pangolins from the Liu et al. study alone was noted on Virological in late January.

Slack / Private Message Drop, p.86 · original PDF · in context

GD/1/2019 (Xiao), which is assembly from NGS SRA data of their pangolin samples, plus confirmation with PCR amplicon sequencing (Sanger/NGS unknown). 4.

Slack / Private Message Drop, p.88 · original PDF · in context

Yes, as you said, some other papers are very nasty, they just down the pangolin sequences from GISAID and do some analysis and published, and without mentioning the source or citing the original papers.

Slack / Private Message Drop, p.88 · original PDF · in context

Completely stupid comments about the Guangdong pangolin CoV...that it may have come from humans.

Slack / Private Message Drop, p.100 · original PDF · in context

She also completely forgets thatt the Guangxi pangolin CoV is also closely related to SARS-CoV-2.

Slack / Private Message Drop, p.100 · original PDF · in context

Also the pangolin RBD is only similar in amino acids - has loads of synonymous differences.

Slack / Private Message Drop, p.100 · original PDF · in context

We are pushing to get the sequence data from the reports on the pangolins, but do not have currently, clearly that isvery important to incorporate.

Slack / Private Message Drop, p.112 · original PDF · in context

Iagree it was mysterious - really mysterious - but then some pangolin viruses came around and mystery solved.Clearly not Bayesians.

Slack / Private Message Drop, p.140 · original PDF · in context

Proposing that all the bat and pangolin sequences are fraudulent and hence SARS-CoV-2 is a lab construct is - well, absurd.

Slack / Private Message Drop, p.163 · original PDF · in context

I'm not even going to go there - I have no concerns about the bat or pangolin data so simply ignoring all of that is just dumb (well, that data invalidates their findings, so of course, I get it).

Slack / Private Message Drop, p.171 · original PDF · in context

I haven't looked at the pangolin data - I'm not quite sure where the raw data is since I believe it was all uploaded tothe Chinese data portals.

Slack / Private Message Drop, p.178 · original PDF · in context

Let me make this very clear: the Guangdong pangolin viruses have been sequenced multiple times by multiple groups.

Slack / Private Message Drop, p.178 · original PDF · in context

Plus there are Pangolins from Guangxi that have been sequenced.

Slack / Private Message Drop, p.178 · original PDF · in context

She also persistently claims that all the pangolin sequences were all derived from the one in the Viruses paper (pre-pandemic of course) which is untrue: there's aseparate assembly in Tommy's paper.

Slack / Private Message Drop, p.178 · original PDF · in context

The pangolin viruses were Sanger sequenced here and this paper clearly shows that these animals are sick: https://www.biorxiv.org/content/10.1101/2020.06.22.164442v1

Slack / Private Message Drop, p.179 · original PDF · in context

The pangolin viruses from the Viruses paper were first assembled in that Virological post.

Slack / Private Message Drop, p.179 · original PDF · in context

But fucking Alina has managed to sow doubt by linking it to those dodgy pangolin papers.

Slack / Private Message Drop, p.179 · original PDF · in context

Only need to assemble one of the remaining pangolin CoVs, which has a huge dataset.

Slack / Private Message Drop, p.184 · original PDF · in context

The argument that not having a close relative argues against natural origins is bonkers.

Slack / Private Message Drop, p.217 · original PDF · in context

Alina is talking about the pangolin sequences where there's overlap in the data used - as described in Eddie's paper.

Slack / Private Message Drop, p.228 · original PDF · in context

In this paper they clear show the pangolins are sick and they Sanger sequenced the spike protein.

Slack / Private Message Drop, p.230 · original PDF · in context

Beyond the accusations that the bat and pangolin sequences are fraudulent is the whole FCS is a :unicorn_face: BSand that no one has ever seen a FCS generated that way before.

Slack / Private Message Drop, p.234 · original PDF · in context

Chan has used Twitter to make increasingly strong claims about the origin of SARS-CoV-2, in particular that it may be of lab rather than natural origin.Of course, Dr.

Slack / Private Message Drop, p.234 · original PDF · in context

Tommy also says that Ian Wilson has shown that the Guangxi pangolin virus binds well to human ACE2.

Slack / Private Message Drop, p.236 · original PDF · in context

Tommy has 6 SARS-CoV-2 sero-positive pangolins that are currently being metagenomically sequenced.

Slack / Private Message Drop, p.245 · original PDF · in context

Tommy has 6 SARS-CoV-2 sero-positive pangolins that are currently being metagenomically sequenced.

Slack / Private Message Drop, p.280 · original PDF · in context

*11 November 2020* Editor's Note: Readers are alerted that concerns have been raised about the identity of the pangolin samples reported in this paper and their relationship to previously published pangolin samples.

Slack / Private Message Drop, p.280 · original PDF · in context

The second Eddie quote also pertinent in light of Xiao et al.editors note *11 November 2020* Editor's Note: Readers are alerted that concerns have been raised about the identity of the pangolin samples reported in this paper and their relationship to previously published pangolin samples.

Slack / Private Message Drop, p.280 · original PDF · in context

Alex mentioned Trevor, Relman and others that are pushing back on conventional wisdom and natural origins.

Slack / Private Message Drop, p.290 · original PDF · in context

Oh - I have just seen what you just said - Malaysia is the same as the Pangolin at 6049 where it differes from WA1

Slack / Private Message Drop, p.299 · original PDF · in context

It is part of the pangolin which is more divergent than RmYN02

Slack / Private Message Drop, p.300 · original PDF · in context

Given it is synonymous and the pangolin has loads of other mutations in that area it must be coincidence.

Slack / Private Message Drop, p.300 · original PDF · in context

Yeah, clearly a lot more cases going around at that time than was appreciated - and obviously not (directly) linked tothe seafood market.

Slack / Private Message Drop, p.301 · original PDF · in context

Weare putting a special bit for pangolin to require 3 of the mutations and no wildtype at these sites to make sure there are no mis-classifcations.

Slack / Private Message Drop, p.332 · original PDF · in context

I can't quite figure out if pangolin actually assigned it to that lineage - the question was asked earlier, but no reply yet

Slack / Private Message Drop, p.332 · original PDF · in context

Interesting difference between SC1 and SC2 is that it was pretty darn quick in the former - essentially happened right after the jump from intermediate hosts.

Slack / Private Message Drop, p.339 · original PDF · in context

@Eddie Holmes It's the GD pangolin - there's that little bit in the RBD where the pangolin blue line is above the green RaTG13 line in Spike.

Slack / Private Message Drop, p.349 · original PDF · in context

I don't think you'd expect this from an imported packet of frozen pangolin.

Slack / Private Message Drop, p.368 · original PDF · in context

The statement about pangolins is ridiculous...and then they throw in the military links....

Slack / Private Message Drop, p.407 · original PDF · in context

New complete genome tree inc. the Cambodian and new pangolin sequence which is from Yunnan.

Slack / Private Message Drop, p.439 · original PDF · in context

I was quite happy with just talking about the natural origins based on the available bat and pangolin sequences but obviously that doesn't address these arguments.

Slack / Private Message Drop, p.489 · original PDF · in context

Must be what Linfa used in the pangolins, although I assumed they were Thai pangolins as the bat virus in that paper is from Thailand.

Slack / Private Message Drop, p.498 · original PDF · in context

Now more focused on the new genomes and what they mean for natural origins.

Slack / Private Message Drop, p.517 · original PDF · in context

The parents of that patient have a link to a different wet market in Wuhan.

Slack / Private Message Drop, p.533 · original PDF · in context

(iii) I'm guessing a lot ofpeople have links to various wet markets.

Slack / Private Message Drop, p.533 · original PDF · in context

The crap about stopping work on bat/animal CoVs is Alina's revenge for all the natural origins proponents that have called out her bullshit.

Slack / Private Message Drop, p.543 · original PDF · in context

We have fixed this now in the latest pangolin so P.1s will only be called based on having 5 or more of the defining mutations.

Slack / Private Message Drop, p.549 · original PDF · in context

These should include: o A pure zoonosis event with/without intermediate host; o Infection at a sampling site of a lab employee or of some accompanying non-lab personnel; o Infection during transport of collected animals and/or samples; o Lab Acquired Infection (LAI) in one of the laboratories in Wuhan; o Lab-escape without LAI, for instance via waste handling or animals that escaped or were disposed of inappropriately.

Slack / Private Message Drop, p.565 · original PDF · in context

Both the possibility of a zoonotic spillover from animal hosts and that of a laboratory accident need independent, expert investigation -- and it is time for a new team to seriously tackle the laboratory hypothesis.

Slack / Private Message Drop, p.572 · original PDF · in context

The WHO-China investigation team, focused on zoonotic spillover, is writing a report, which the director general ofthe WHO, Tedros Adhanom Ghebreyesus, says will be released the week of March 15.ADAnother hypothesis, that the pandemic was ignited by some kind of laboratory leak or accident, is denied by China.

Slack / Private Message Drop, p.572 · original PDF · in context

Of course, that bats may be passing the virus to pangolins does nearly show that virus jump between species in nature.

Slack / Private Message Drop, p.589 · original PDF · in context

This paragraphs sticks out "Next, to address the question of whether those two sites are evolutionarily conserved,we generated a phylogenetic tree of the seven patient samples linked with the Huanan Seafood Wholesale Market(hereinafter named as the Market) and the related coronaviruses from animal reservoirs by nucleotide sequence alignment [14].

Slack / Private Message Drop, p.592 · original PDF · in context

Raises a question as to whether pangolins are true reservoirs of multiple CoV lineages (possible) or just occasionally getting infected via spillovers - presumably from bats.

Slack / Private Message Drop, p.611 · original PDF · in context

The key point is thatit won't just be bats and pangolins....

Slack / Private Message Drop, p.611 · original PDF · in context

Asher is a buffoon - he's literally talking about pangolins and bats *mating*.

Slack / Private Message Drop, p.618 · original PDF · in context

The guy that Pompeo is relying on for his information about WIV is the same guy (Asher) that thinks that pangolinsmated with bats.

Slack / Private Message Drop, p.623 · original PDF · in context

IIRC there is published epi info that at least some of the lineage A cases frequented wet markets.

Slack / Private Message Drop, p.626 · original PDF · in context

I'd like to know if that map of the Huanan market is reliable.

Slack / Private Message Drop, p.628 · original PDF · in context

Yeah - it's a seafood market, but I'm glad GG admitted that they were selling wild illegal animals there.

Slack / Private Message Drop, p.634 · original PDF · in context

Lineage A viruses were linked to wet markets too and those are ancestral.

Slack / Private Message Drop, p.638 · original PDF · in context

So the virus has to find one wet market -add 3 snps to become lineage B then find the Huanan market.

Slack / Private Message Drop, p.638 · original PDF · in context

Also good to point out that the fact that some of the earlier cases in Wuhan also had links to other Wet Markets - nota stretch to believe that a batch of infected or cross-infected animals was distributed from South China seedingHuanan and other markets.

Slack / Private Message Drop, p.643 · original PDF · in context

The culling of the animals atthe Huanan Market was a perfectly reasonable thing to do - in fact the correct thing to do from a Pubic Healthstandpoint.

Slack / Private Message Drop, p.643 · original PDF · in context

Qun2020:- Worth revisiting in light of new info about lineages A and B. actually has the information that the lab leak group want to dismiss- the early cases were associated with other wet markets not just the Huanan Wet Market. [shared file(s): nejmoa2001316.pdf]

Slack / Private Message Drop, p.644 · original PDF · in context

Here is the key Table about the early cases - All the Huanan Market cases lineage B.

Slack / Private Message Drop, p.644 · original PDF · in context

The other early ones linked toother wet markets lineage A. @Andrew Rambaut or @Eddie Holmes may have more detailed info.

Slack / Private Message Drop, p.644 · original PDF · in context

Interestingly also there is a Malaysian case with exactly the same WA1 haplotype (Malaysia... pangolins...).

Slack / Private Message Drop, p.644 · original PDF · in context

This figure from the report is pretty interesting - breeding of putative intermediate hosts all around Wuhan. [shared file(s): Screen Shot 2021-03-29 at 7.50.43 PM.png]

Slack / Private Message Drop, p.656 · original PDF · in context

That line that bisects the cluster is the main river - WIV is South-East of that river, Huanan market North-West

Slack / Private Message Drop, p.657 · original PDF · in context

Good questions My take on the whole thing is that they clearly think there's an intermediate host and they are holding up the marketas an example of the trade that leads to this transmission Daszak clearly thinks it the market which is why he sent me the video There's a lot on the market in the main doc - 2 journos told me they had the same impression

Slack / Private Message Drop, p.657 · original PDF · in context

Amy: https://www.nature.com/articles/d41586-021-00865-8"Plenty of animals were sold at the Huanan market.

Slack / Private Message Drop, p.660 · original PDF · in context

See how this starts North (right where Huanan market is) of the Yangtze river and then moves South (where WIV) is.This is exactly the same pattern we see from the confirmed case data.

Slack / Private Message Drop, p.662 · original PDF · in context

There's definitely a CoV in some of the new pangolin samples Tommy has.

Slack / Private Message Drop, p.671 · original PDF · in context

I'm also confused by the WHO report from November which said their were live wild mammals present at the market prior to Dec. 31, 2019 and the latest study team report which takes the market authority and one Huanan manager'sword for it that there were no live wild mammals at the market at that time.

Slack / Private Message Drop, p.679 · original PDF · in context

The owner of the Huanan market and this other market himself is quite problematic from a potential wildlifetrafficking perspective, but I can't say much about what I know there at the moment.

Slack / Private Message Drop, p.679 · original PDF · in context

They were there when the WHO team was there at Huanan, but apparently no one talked to them.

Slack / Private Message Drop, p.679 · original PDF · in context

Everyone around that we spoke with knew they kept pangolins there.

Slack / Private Message Drop, p.680 · original PDF · in context

From Zhang "More works are needed for the intermediate hosts.

Slack / Private Message Drop, p.685 · original PDF · in context

Finally had some time to read the pangolin paper in Frontiers.

Slack / Private Message Drop, p.696 · original PDF · in context

Need to navigate the animal use regs, but it's trap, swab, tag (assuming we can find a soft spot) and release so will beinteresting to see if West African pangolins have CoVs.

Slack / Private Message Drop, p.697 · original PDF · in context

Really interesting but I haven't fully got my head around it - basically it means that the bat-like NTD is sub-optimal for humans, B.1.1.7 has converged on whatever the pangolin has as an adaptation to humans (given that B.1.1.7 is the most human adapted virus yet).

Slack / Private Message Drop, p.699 · original PDF · in context

Billy's in for a surprise when the new pangolin data is published

Slack / Private Message Drop, p.709 · original PDF · in context

No surprise that Ape Boy fails to remember that the first Guangdong pangolin CoV was published BEFORE the pandemic started.

Slack / Private Message Drop, p.710 · original PDF · in context

I love to think of the Grand Wizard and myself as the Natural Origin Police.

Slack / Private Message Drop, p.713 · original PDF · in context

Impossible to _honestly_ wave away the fact that 2/3 of the early cases were associated with wet markets, just like the two SARS1 outbreaks.

Slack / Private Message Drop, p.717 · original PDF · in context

He's certainly right about rescue centres (which is of course where the pangolins ended up).

Slack / Private Message Drop, p.727 · original PDF · in context

The first one, about The Boss of the Huanan market, is coming together.

Slack / Private Message Drop, p.736 · original PDF · in context