Are there laws of evolution that are unique to SARS-CoV-2 related coronaviruses? Or were sequences invented to conceal its artificial origin? This is trivially easy with a system based on trust.
Have you read the earlier piece? There's more about the geopolitical backdrop in this, although when it comes to some of those aspects I'm having to speculate.
Bat cell lines have so far proven difficult to infect with any virus, perhaps because they express IFN at too high levels. There's a project to set up a vivarium for insectivorous bats at the NIH Rocky Mountain Lab for live infectivity experiments. This has ofc attracted controversy, and now the guy driving it - Vincent Munster - has got himself into some trouble with the law. Idk the status.
ACE2/RBD binding studies that have been done have generally shown only weak or no binding to bat ACE2. Banal-103 (which has aa identical RBM to BANAL-52) has been shown not to bind its host species (R. pusillus) ACE2. BANAL-52 is supposedly hosted by R. Malayanus for which no ACE2 sequence is yet available. Idk why not -you'd think they would collect the bat sample and sequence this gene too.
Zhengli Shi claims bat ACE2 is highly diverse, even within the same species there are significant regional differences. But of course she would...
It always seemed suspicious to me that SARS2 bound very weakly to RA bat ACE2, if direct infection from a bat to a human was one of the likely sources of the outbreak. I understand that this might be because bats generally have receptors that are very good at hiding from viruses, due to evolutionary pressure of living in dense colonies, so the spikes have to evolve extreme binding efficiency if the viruses are to propagate, and once they are exposed to other species, they might run rampant. I guess, according to this theory, weak binding is all that is needed, perhaps due to density of individuals?
Then the fact that the spike binds more strongly to human ACE2 than any other species intermediate host theory would seem to require either a minimal period of circulation in intermediate hosts, or circulation in intermediate hosts with very similar ACE2 to humans, e.g., humanised mice. This presents a further mystery - the virus ought to have been at least as transmissible in intermediate hosts as it was in humans, so why was there no panzootic, only a pandemic?
It might make more sense if SARS-CoV-2 had been an endemic human disease which started to spill over into bats ,but is still not well-adapted to them.
Most sarbecovs don't bind ACE2 (including bat ACE2) it's not their natural receptor (which is unknown). They're enteric, not respiratory viruses, is there a reason they would evolve to bind ACE2? To do so requires gaining inserts in the RBM, fortuitous events similar to the way the FCS was acquired - not regular evolution by substitution.
The first ACE2 binders were only claimed in 2013 by WIV and AMMS, and they remain the only two groups to have claimed to have isolated SARS-1 like viruses. These also look suspiciously like lab-made chimeras.
This really seems like the French government owes information to the public.
Have you read the earlier piece? There's more about the geopolitical backdrop in this, although when it comes to some of those aspects I'm having to speculate.
https://www.sarsisterrorism.org/p/a-french-enlightenment
No. I will.
A great exposition. Many thanks for all your hard and insightful work. Adrian G.
fantastic (and terrifying) piece.
Has anyone tried constructing live Banal-52 from the genome and seeing if it infects bat gut cells?
Bat cell lines have so far proven difficult to infect with any virus, perhaps because they express IFN at too high levels. There's a project to set up a vivarium for insectivorous bats at the NIH Rocky Mountain Lab for live infectivity experiments. This has ofc attracted controversy, and now the guy driving it - Vincent Munster - has got himself into some trouble with the law. Idk the status.
ACE2/RBD binding studies that have been done have generally shown only weak or no binding to bat ACE2. Banal-103 (which has aa identical RBM to BANAL-52) has been shown not to bind its host species (R. pusillus) ACE2. BANAL-52 is supposedly hosted by R. Malayanus for which no ACE2 sequence is yet available. Idk why not -you'd think they would collect the bat sample and sequence this gene too.
Zhengli Shi claims bat ACE2 is highly diverse, even within the same species there are significant regional differences. But of course she would...
It always seemed suspicious to me that SARS2 bound very weakly to RA bat ACE2, if direct infection from a bat to a human was one of the likely sources of the outbreak. I understand that this might be because bats generally have receptors that are very good at hiding from viruses, due to evolutionary pressure of living in dense colonies, so the spikes have to evolve extreme binding efficiency if the viruses are to propagate, and once they are exposed to other species, they might run rampant. I guess, according to this theory, weak binding is all that is needed, perhaps due to density of individuals?
Then the fact that the spike binds more strongly to human ACE2 than any other species intermediate host theory would seem to require either a minimal period of circulation in intermediate hosts, or circulation in intermediate hosts with very similar ACE2 to humans, e.g., humanised mice. This presents a further mystery - the virus ought to have been at least as transmissible in intermediate hosts as it was in humans, so why was there no panzootic, only a pandemic?
Good questions.
It might make more sense if SARS-CoV-2 had been an endemic human disease which started to spill over into bats ,but is still not well-adapted to them.
Most sarbecovs don't bind ACE2 (including bat ACE2) it's not their natural receptor (which is unknown). They're enteric, not respiratory viruses, is there a reason they would evolve to bind ACE2? To do so requires gaining inserts in the RBM, fortuitous events similar to the way the FCS was acquired - not regular evolution by substitution.
The first ACE2 binders were only claimed in 2013 by WIV and AMMS, and they remain the only two groups to have claimed to have isolated SARS-1 like viruses. These also look suspiciously like lab-made chimeras.
https://zenodo.org/records/13476370