So @Daoyu15 pointed to this great preprint that once again confirmed that RaTG13 doesn't bind well to bat ACE2. The beauty of this work is that it tested ACE2 of the very species RaTG13 was allegedly sampled from, R. affinis.
As this figure shows, RaTG13 is really bad at binding to R. affinis bat ACE2. Even the T403R mutation that makes it bind really well to human ACE2 is helpless when it comes to R. affinis ACE2. Weird? Weird.
3/6
What is even more weird is how well it binds to human ACE2. Sure it's no champ like SARS2 but RaTG13 binds to human ACE2 just 1/2 as well (100k cells/well), which is also about 8x better than SARS2 does to R. affinis ACE2 (12k cells/well) (see above fig.)
4/6
So RaTG13, what gives? Where'd you learn to bind to human ACE2 so well? Humanized mice, perhaps?
Or were you the the virus that infected the Mojiang miners?
5/6
Finally, are you really the same as 4991 or are you a hair different in your spike protein? About 1.1% different so that the difference between your S gene and that of SARS1 would be 1.1% different than the diff reported for 4991 and SARS1 in 2019?
Another rabbit hole on the topic of SARS2 as a potential pan-coronavirus vaccine candidate. This time it was prompted by @gdemaneuf pointing out several papers that say SARS2 spike might bind not just to ACE2 but also to the MERS receptor, DPP4.
1/3
There have been several papers just after the outbreak of SARS2 that hypothesized that it could also invade immune system cells via DPP4 receptor, mostly based on in silico modeling. Then a couple papers reported that in actual experiments it doesn’t and this topic died down
2/4
But even if it doesn’t bind to the MERS receptor, the presence of those residues in its spike is intriguing, as they could come from someone trying to make it bind and/or trying to generate neutralizing antibodies against those key residues with a goal of neutralizing MERS.
3/4
Just so that we’re clear — I am not saying we should dismiss any COVID vaccine concerns. Absolutely not! We should debate any potential issues and closely monitor any actual ones. So far there do seem some rare minor issues and ultra-rare major ones (deaths, clots).
1/5
Not all vaccines are equal. Some are better than others. I am a huge fan of mRNA ones, I fully admit. I’ve been a fan of mRNA technology for many years (back when it was just invented/considered for use in Yamanaka factors delivery which are my main passion).
2/5
Vaccines seem like a perfect fit for the mRNA technology, especially in a pandemic where you need very quickly adapt to novel strains. I actually hope we can squeak by without new boosters, but for that we need a coordinated world-wide effort to eradicate SARS2 ASAP.
3/5
So some COVID vaccine alarmist have been quoting the study by @manorlaboratory out of Salk that SARS2 spike alone can cause cell damage. But that’s not what the study has shown!
1/4
Those were not lone spike proteins, those were HIV-like virions encoding SARS2 spike. I.e. entered the cells expressing ACE2 and once inside expressed their proteins and maybe even integrated into cell genome (not sure if they used integrase-deficient retroviruses or not).
2/4
Maybe the confusion is due to the lax wording by the popular science article describing the study:
AAA SNAKES ON A PLANE, I mean
SPIKES IN MY BRAIN AAA!!!
The latest Covid vaccine fear is that spike proteins produced by the vaccine will get out of the cells, get into the bloodstream, and travel to the brain causing prion-like pathology.
1/4
While there are some data that free-floating spike proteins (or just their fragments) seem to be detected in the blood the first couple of days after vaccination, the amounts detected are minuscule, around 70 pg/mL. A picogram is 1e-12 gram.
2/4
Moreover, free-floating spikes cannot get inside cells on their own, and even if they could, any potential prion-like effects of spikes are pure conjecture at this point: nothing of sort has yet been observed — neither in vitro or in vivo.
3/4