Work by Shi and colleagues on humanizing bat CoVs dates back to at least 2007.
From:
onlinelibrary.wiley.com/doi/10.1002/bi…
Paper:
jvi.asm.org/content/82/4/1…
This early research only used chimeric Spike constructs in pseudovirions.
Baric did full CoVs the next year.
Comparative analysis of SARS-CoV-2 binding to ACE2 across hundreds of mammalian species reveals the strongest affinity is for *human and primate* ACE2.
Moreover, there is little to no selection pressure toward hACE2 by the virus. It *already worked*.
This is exactly as expected if the viral RBD was chosen from a set of sampled strains based on its affinity for human ACE2.
It is *not* expected for natural origin. That should produce selection toward hACE2 from bat ACE2. Instead, we actually see selection *toward bat ACE2*.
In other words: this random weirdly-shaped Spike RBD was *barely clinging* to its ability to bind bat ACE2 and circulate among bats. It was under selection pressure to bind bat ACE2 better.
Meanwhile it *randomly happened* to have very high affinity for human ACE2 *already*.
The probability of this being coincidence is minuscule. Hardly any humans living nearby have antibodies to SARS-like CoVs. This RBD was not from a human virus.
It came from a low-fitness bat virus that just so happened to be a great candidate for human emergence studies.
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