Thread by @jpglmrodrigues

1/ One of the mutations reported in the new variant of SARS-CoV-2 found in minks in Denmark - Y453F - sits right in the middle of the interface with the ACE2 receptor, interacting with H34, a residue we and others marked as an important "hotspot" for the interaction.

https://twitter.com/KasperKepp/status/1324373146489806851

2/ Unfortunately, we only have a partial sequence of ACE2 for the American mink (Neovison vison), which is the species that is bred for its fur, according to Wikipedia. But if we look at its European cousin (Mustela lutreola), we find interesting mutations in their ACE2 variant:

3/ There is D30E, which we & others predict enhances affinity since it stabilizes a salt-bridge w SARS-CoV-2 Spike K417. Then, we have H34Y, which is particularly interesting in the context of this new viral variant. Here's the relevant part of the aln with our ACE2:

4/ Looking our models of ferret ACE2 (a very similar cousin of the minks), which are one of highest scoring species in our study, a Y453F mutation on the viral protein can help pack the interface a little better. Have a look at our models yourself, here: unstructuredbio.com/ace2-animal-mo…

5/ On the other hand, exps with human ACE2 suggest that increasing hydrophobicity around position 34 (e.g. H34L) is a good move to make the viral spike stick better. So, the Y453F mutation might help the virus stick well enough to both ours & mink's ACE2 to promote transmission.

6/ For more details about our modeling and how we think these and other mutations influence the binding of the viral spike to ACE2, read our preprint and keep an eye out for the peer-reviewed version soon out in @PLOSCompBiol.

biorxiv.org/content/10.110…

7 & last/ If you needed yet another reason not to support these farming practices, which cram thousands of animals together in small cages and probably serve as an incredible Petri dish for the virus to evolve, here you go. Now we might have to catch up because gloves & jackets.

👏Thanks @LindorffLarsen for bringing this mink variant story up to our attention!