
Originally Posted by
exchemist
It is certainly possible that the virus might have escaped from the Wuhan lab. But there seems to be no reason, from its make-up, to suspect that the virus is engineered in any way.
The biochemical evidence for a direct "human-based" source for SARS-CoV-2 is derived primarily on its binding affinity for the human ACE-2 receptor, as determined from the original virus strain which emerged from China. Bats are still believed to be the primary source, but the closest sequence homology found so far is about 97%, too different to allow a direct jump. Manipulation of some related virus however, by gain-of-function studies, could have easily resulted in this human pathogen without an intermediate animal host, which has not been found despite enormous effort. It should be apparent that a gain-of-function origin for a virus is a form of engineering, providing a mechanism, and relying on the course of viral evolution by mutation to select for the most infectious strains.
As mentioned in the first post, the original virus has binding affinity for the human ACE-2 receptor in the nanomolar range. This binding affinity has been experimentally determined to be 5-20 times higher than that of the original SARS virus (1). Thus the data indicate that the current virus affinity for its primary human receptor is higher, on average, by an order of magnitude - a non-trivial difference to be certain.
It should also be clear that it is unlikely to have evolved with such a high affinity for the human receptor in a non-human animal, all of which would have ACE-2 receptors significantly different structurally from humans. While the virus is capable of infecting other animals (cats, etc.), there is no evidence of significant pathology or transmissibility in these animals, almost certainly due to a large decrease in affinity for non-human receptors. High receptor binding affinity is critical for significant viral replication and pathogenicity.
Quoting from (1):
"Wrapp et al. showed that the S protein of SARS-CoV-2 binds to the ACE2 peptidase domain (ACE2-PD) with a binding affinity clearly higher than that of SARS-CoV. The dissociation constant KD of SARS-CoV-2 is 14.7 nM, 10–20 times lower than that of SARS-CoV..."
end quote
Again, such a direct high affinity upon its appearance in humans suggests a non-natural origin. To appreciate the nature of gain-of-function aspects in viral evolution, the increase in virulence of this virus as it spreads among the human population is demonstrated by the various strains which have replaced the original in the pandemic. Some of the more infective strains are showing higher ACE-2 binding affinities, a classic example of gain-of-function (2), and is the very reason for conducting such studies - to find out how bad it can get. And we are surely finding out. To clarify, we are currently seeing gain-of-function applicability in the global pandemic as more and more infective strains evolve, primarily in those who have not be vaccinated or previously infected.
Quoting from 2 :
"It was shown that S-protein mutation D614G may impact SARS-CoV-2 transmissibility rate due to higher affinity for olfactory epithelium and it was shown to have higher transmissibility in animal models..."
end quote
Adding to the questionable origin of this virus is, as previously posted, that the Chinese were working with knockout mice where their ACE-2 receptor was replaced with the human version. This represents an excellent approach to gain-of-function studies, and there could be no other reasonable purpose for creating such a murine model. Clearly this was a very bad idea. It seems like a very good reason why they are extremely negative regarding a comprehensive study on its origin.
And with Dr. Anthony Fauci indicating he no longer believes it has a natural origin, there is clearly growing evidence which strongly suggests that a laboratory derivation of this virus is more than likely.
"Does SARS-CoV-2 Bind to Human ACE2 More Strongly Than Does SARS-CoV?"
1.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7433338/
"Emerging SARS-CoV-2 variants of concern and potential intervention approaches"
2.
https://ccforum.biomedcentral.com/ar...54-021-03662-x