What Wade says is irrelevant. You made a claim about the data; you’re making it abundantly clear that you didn’t look.
What Wade says or doesn’t say is irrelevant. You claimed this literally as a fact. Now you reveal that you never looked?
One does not need to be an expert in the field. If you disagree, is Wade an expert? If not, why are you parroting his claims as fact without checking them?
You made the claim yourself, Gil. You misrepresented hearsay that you didn’t check as established fact:
Why would you claim that this is a fact when you don’t know it to be a fact? Why would you qualify it with
When you can’t even state which viruses would be included in that group?
Sorry, I missed that detail. How would you suppose Wade determined which betacoronaviruses were “SARS-related” and which were not? That seems like an arbitrary distinction, since clearly, all of the betacoronaviruses are related.
It is indeed arbitrary. I would say that the distinction was intelligently designed to fool those who won’t bother to check and to facilitate waffling when challenged with the data.
As a non-biologist, what is the value in just letting the intelligence communities look into the actual circumstances around the origin of SARS-CoV-2 rather than trying to settle it via biology? Is this sort of a “when all you have is a hammer, everything is a nail” or do we really think molecular biology and genetics alone are going to be able to solve the problem?
[edit] or is it a “anything can turn into an ID vs evolution fight”?
Ideally, such an investigation would be fruitful and apolitical. However, there is very little chance that such an investigation would be ideal!
Speaking only for myself - the biggest gap that currently exists in the natural origin explanation is the current absence of a natural “mutation trail” of the virus going from bat or pangolin populations to human. Trails were found for SARS and MERS, but no such trail has yet been discovered for SARS-CoV-2. There are hints here and there, but the clarity of the path just isn’t there yet. It should be noted that we don’t have anything close to a clear trail for Ebola, either, but Ebola doesn’t carry the same political baggage with it.
Because biology, specifically the nested hierarchies constructed from sequence data, is the strongest evidence we have.
And these trails are routinely illuminated by new data.
A highly pertinent example of this is the hypothesis that the “Russian Flu” of the 1890s was caused by the jumping of a bovine coronavirus that is closely related to OC43, one of the four that routinely cause mere common colds now. The human and bovine viruses appear to have diverged in about 1890 (full text): https://jvi.asm.org/content/79/3/1595
Here’s a more layperson-friendly review that includes this (full text):
I don’t see why this is interesting. The minimal furin cleavage motif is R-X-X-R, where “R” is arginine and “X” is another amino acid, usually arginine or lysine. The furin cleavage site of SARS-CoV-2 is R-R-A-R, while that of MERS-CoV is R-S-V-R, so whether CGG or another codon is used for arginine seems irrelevant, what matters is that we get arginine. More so, “least popular (preferred)” doesn’t mean “cannot be used”, so we finding CGG being used for arginine in a furin CS is insignificant.
Furthermore, I think you are overgeneralizing here. Its true that CGG at the level of whole genomes is least preferred but when we look at individual genes and coronaviruses that no longer applies to a large extent. For example, MERS-CoV and SARS-CoV-2 prefer to use CGG for arginine for their M genes over CGA. See this charts:
There are dual CGG repeats in other betacoronaviruses. However none is found in the furin CS of sampled betacoronaviruses apart from SARS-CoV-2, but this point is moot because a CGG-CGG for two successive arginine residues in a furin CS is not necessary. There are other furin-susceptible codon combinations without a CGG-CGG in other coronaviruses like the one in the betacoronavirus MERS-CoV.
Human furin proteins recognize the motif, R-X-X-R, not CGG-CGG (that’s why they can recognize the furin CS in MERS-CoV as well). In addition, dual CGG repeats are found in all coronavirus genomes. That one of such repeats encoding arginine found its way into the nucleotide sequence of the furin CS (most likely through recombination) of SARS-CoV-2 is completely unsurprising under outside-laboratory emergence.
There is no “preferred human codon”, but a motif for our furins.
True, but this could also happen naturally. Evidence is gathering that the RRAR furin CS was most likely derived via recombination with another bat coronavirus. One line of evidence comes from the discovery of a bat coronavirus closely related to SARS-CoV-2 with polybasic amino acids at the S1/S2 junction. Of course, these polybasic amino acids didn’t constitute a furin cleavage site, but considering that the same region is vacant in other close relatives, this raises the probability that the furin CS was derived naturally via recombination. You can read here:
SARS-related means Severe Acute Respiratory Syndrome-related. SARS-CoV-2 and SARS-CoV cause SARS, so does MERS-CoV. The twist here is that when MERS-CoV causes SARS, for some some reason its called MERS even though SARS and MERS are the same disease.
MERS-CoV is a SARS-related betacoronavirus because its causes SARS/MERS, but it is distantly related to SARS-CoV-2 and SARS-CoV.
We can answer three questions based on the findings of both studies (and others).
First, does a furin cleavage site exist in the spike protein of SARS-COV-2 and MERS-CoV? The answer is yes. The first study draws a strange conclusion though. It says:
But this runs counter to its findings below:
Its true that R-x-x-R motif was inefficiently cleaved, but it was cleaved nonetheless indicating that the region upstream of the S1/S2 cleavage site in MERS-CoV is indeed a furin cleavage site. This finding simply indicates that the wild-type R-x-x-R motif of MERS-CoV is a poor substrate for human furins, while that of SARS-CoV-2 is a better substrate. This is evident because the mutagenesis experiment which was done next turned the tables around: a single amino acid substitution was introduced into the wild-type R-x-x-R motifs of SARS-CoV-2 and MERS-CoV, which significantly lowered and increased the efficiency of cleavage of SARS-CoV-2 and MERS-CoV mutant R-x-x-R motifs respectively. See below:
This corroborates my conclusion that wild-type MERS-CoV R-x-x-R motif is a poorer substrate for human furins, but it is still a furin CS.
Second, is preprocessing of the S1/S2 by furin via cleavage necessary for MERS-CoV entry into susceptible cells? The answer is no (based on the second paper) and the same applies to SARS-CoV-2 (based on another paper linked below). Of course, if the R-X-X-R motif of MERS-CoV is a poor substrate for human furins, we would expect it to mediate little or no viral entry via furin-dependent pathways and vice versa for SARS-CoV-2.
Third, is the fact that the second arginine in the R-X-X-R (R-R-A-R) motif is highly advantageous to SARS-CoV-2 because it increases its infectivity surprising under an outside-of-the-lab emergence? No. Furin preprocessing of the spike protein certainly improves the efficiency of cellular infection, but as the last study I cited showed, it seems not to be essential for that purpose. Its likely the earliest strains of SARS-CoV-2 derived a poorly recognized furin CS via recombination from another bat coronavirus, but used furin-independent, TMPRSS2-dependent pathways to make the jump into human populations. After a while, amino acid substitutions to its R-X-X-R motif made it a better substrate for human furins, giving the virus a boost in infectivity, thus, contributing to its current pandemic status.
I found this study which looked at natural polymorphisms in the furin CS of SARS-CoV-2 isolates from patients. Lo and behold, it showed that SARS-CoV-2 can still spread in the absence of its furin CS.
The more I examine this issue, the likelihood of a lab leak just keeps dropping. In any case, let’s hope better evidence comes along to conclusively settle this issue.
Interesting. I would very much like to know more about this. More precisely, I would like to know what other documented outbreaks already originated at Wuhan and, more importantly, what were their natural histories. Do you have some references on these issues?
Then prepare for a lot of Googling! The current literature is swamped with articles related to the current outbreak, so look for sources prior to 2019. I found this one (below) by following the references from a current article.
source:
Shuo Su, Gary Wong, Weifeng Shi, Jun Liu, Alexander C.K. Lai, Jiyong Zhou, Wenjun Liu, Yuhai Bi, George F. Gao,
Epidemiology, Genetic Recombination, and Pathogenesis of Coronaviruses,
Trends in Microbiology,
Volume 24, Issue 6, 2016, Pages 490-502, ISSN 0966-842X, Redirecting.
(https://www.sciencedirect.com/science/article/pii/S0966842X16000718)
I just had someone on my Facebook page who supports the lab leak theory agree it was a conspiracy theory, and then criticize me for giving the term “conspiracy theory” a bad connotation.
