So, Flo Debarre et al’s raccoon dog analysis that has caused such a media frenzy has been released and what does it show ?
Not much 🧵
2/ Essentially, it confirms Gao et al’s preprint analysis that there was nuc acid from animals in addition to humans in the samples 👇 (no surprise there)
It adds some species specific info
3/ The analysis is crude, and taxonomic attribution method naïve
They rely on seq assembly, which miss a lot of info
They use numbers of assembled contigs as a metric for quantity of species specific material
This is semi-quantitative at best (due to the vagaries of assembly)
4/ Even then, they fail to see if the species specific material correlates with numbers of SARS2 reads, which is inexplicable
5/ They apparently identify a potentially new subspecies of raccoon dog – this would worth following up for forensic purposes, but bafflingly they fail to do so
6/ But they also seem to identify new subspecies of masked palm civet, hoary bamboo rat, Malayan porcupine and Amur hedgehog. This could be interesting, or more likely indicates problems with their assembly. Oddly, they fail to follow this up and validate their assembly qualities
7/ Bizarrely, they seem unable to differentiate between DNA and RNA (hint, trying mapping reads to annotated mito genome or nuc genome). This has importance as it can affect estimates of relative species proportions
8/ Tellingly, none of the stalls with raccoon dog nuc acid have a human SARS2 case linked to it (which puzzlingly they fail to mention)
(figure on left from our HSM Zoonosis critique, on right from Debarre et al)
9/ This saga is a case study in the perils of making grandiose claims without having completed the analysis, and of the hubris to embark into a new subject area without specialists (metagenomic) to scrutinize and suggest robust analyses
A link between MERS-CoV pathogenicity and epithelial sodium channel (ENaC) was described in a 2016 proposal by Luis Enjuanes, collaborator of Baric h/t @USRightToKnow
Coincidentally, the human α-ENaC furin cleavage site (FCS) is identical to that of SARS2 🧵
2/ As far back as 2009 it was known that SARS1 spike and E proteins interacted with human ENaC, modulating its activity leading to fluid buildup in the lungs
Fluid buildup (pulmonary edema) is a key symptom of both SARS1 and SARS2
The GOF Executive Order includes no clear ban on US-based GOF research, but kicks the can down the road
Weak gruel unfortunately at this stage, vested interests seem to have inserted themselves 🧵 whitehouse.gov/presidential-a…
@thackerpd @emilyakopp @HansMahncke @ban_epp_gofroc @lewiskamb 2/ While executive focus on GOF is to be welcomed, unfortunately this Executive Order (EO) does not deliver a ban on US GOF research. While it bans funding of dangerous GOF in countries of concern, why does it not do the same in the US ? Why not a blanket ban ?
3/ There is also a ban on GOF in countries with inadequate oversight, but presumably that allows GOF in countries that do pass the oversight test (and what that test is remains to be described)
2/ @quay_dr uploaded our original preprint on March 26
We identified 7 'frozen' SARS2 sequences from UNC, that were basal to other sequences generated at the same time. These could represent early SARS2 strains that had escaped from a research facility
3/ Before uploading the preprint, we sent an email to Dirk Dittmer and Melissa Miller of the Clinical Molecular Microbiology Laboratory, UNC Hospital, regarding the 7 anomalous sequences we had detected from their sequencing facility
Steve Quay @quay_dr and myself have published evidence for a potential lab leak of SARS2 at the University of North Carolina (UNC)
7 genome sequences collected by UNC in 2020-21 are basal (ie 'frozen') indicating a potential lab origin 🧵 zenodo.org/records/150833…
2/ The 7 sequences were collected from Jun 2020 to Jan 2021 and submitted by Dr Dirk Dittmer of the Clinical Molecular Microbiology Laboratory, UNC Hospital
Puzzlingly, they show strong similarities to the SARS2 reference sequence Hu-1, sampled in Dec 2019
3/ On the dates the 7 sequences were collected, they should have accumulated more SNVs than they actually possess, according to the SARS2 molecular clock
I've published a paper on the emerging phenomenon of 'frozen' virus genome sequences, and how they can indicate lab leaks
"Frozen' virus genome sequences are generated from recent outbreaks, but show surprising similarity to historic strains 🧵 mdpi.com/2076-2607/12/1…
2/ The classic example is 1977 'Russian' H1N1 Flu, which re-emerged after having gone extinct in the 50s. Genomic sequences were identical to strains from the 50s, indicating it had been stored for > 20 years before release nature.com/articles/27433…
3/ An alternative scenario of viral host persistence / latency seems unlikely
A clue to its non-natural origin was that only younger people got sick, while older people were immune. This is because the latter had been exposed to H1N1 in the 50s and before pmc.ncbi.nlm.nih.gov/articles/PMC23…
It has been reported German Intel has assessed that COVID19 originated via a lab leak
Swiss paper NZZ reports that our discovery of a MERS-related infectious clone with a chimeric spike from Wuhan sequencing datasets was considered by German Intel 🧵
2/ The study by @humblesci @Daoyu15 @BiophysicsFL @ydeigin @quay_dr and myself was published last year and demonstrated unreported GOF experimentation on novel MERS-related coronaviruses in Wuhan prior to the pandemic fortunejournals.com/articles/disco…
3/ Concerningly, we found evidence that a MERS spike (with FCS) was inserted into a HKU4r-CoV backbone, likely enhancing transmissibility in human cells, as the RBD is expected to have a high binding affinity for the hDPP4 receptor
Here is a thread on the preprint version of the paper: