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Slack / Private Message Drop, p.996 [SLACK_001210] · slack_pm:msg:10390

Date: 2021-09-14 06:27
Type: chat message · slack
recipient: Kristian G. Andersen, Edward C. Holmes, Andrew Rambaut
speaker: Robert F. Garry
Topics: Furin cleavage site and molecular features

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Mutation of two amino acids (K479N and S487T) in palm civet SARS-CoV RBD allows this virus to infect humans (Li, 2008). These changes overcome the species barrier between civets and humans and enable favorable interactions between the RBD and contact residues on human ACE2. Q493 and N501 are the two SARS-CoV-2 residues that have similar interactions with ACE2 as SARS-CoV residues N479 and T487.

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2021-09-14 06:20 Robert F. Garry open

So, the Proline at 681 is important for the O-glycans. S at 681 changes the prediction from three to only one O-linked glycan - as @Kristian Andersen has pointed out this likely is involved in regulation of cleavage - rather than any "glycan shielding." [shared file(s): image.png]
2021-09-14 06:23 Andrew Rambaut open

Interestingly this is actually a R681S mutation
2021-09-14 06:23 Andrew Rambaut open

(i.e., a Delta)
2021-09-14 06:27 Robert F. Garry open

Of course N501 is the a key residue for cross-species transmission. N501T is a key mutation for minks and ferrets. Serine is chemically similar to Threonine.
2021-09-14 06:27 Robert F. Garry

Mutation of two amino acids (K479N and S487T) in palm civet SARS-CoV RBD allows this virus to infect humans (Li, 2008). These changes overcome the species barrier between civets and humans and enable favorable interactions between the RBD and contact residues on human ACE2. Q493 and N501 are the two SARS-CoV-2 residues that have similar interactions with ACE2 as SARS-CoV residues N479 and T487.
2021-09-14 06:32 Robert F. Garry open

R681S - That is interesting - hard to predict the effect on cleavage. The fsc is still there of course, but cleavage could be improved (the S might be a better landing site than the R) or decreased. And, the wild-card of the O-glycans not being there.
2021-09-14 06:34 Andrew Rambaut open

These are the mutations we are seeing (we are not sure how they are linked as they are environmental samples). The last column is me looking outside the SARS-CoV-2 to the bats/pangolins ```S:R102T (21867:G>C) conserved S:D442N (22886:G>A) conserved S:Y449H (22907:T>C) 449F 449G S:N450T (22911:A>C) 450S (RaTG13), 450G S:P499S (23057:C>T) 499S (Cambodian bats) S:N501D (23063:A>G) 501D (RaTG13), 501T, 501V S:N501S (23064:A>G) S:Q506P (23079:A>C) conserved S:P681S (23603:C>T) missing S:V772A (23877:T>C) conserved S:Q779L (23898:A>T) conserved S:L828I (24044:C>A) conserved S:G932D (24357:G>A) conserved S:S937A (24371:T>G) conserved```
2021-09-14 06:35 Andrew Rambaut open

question is - does any of this spike profile make you think it might be in a non-human host?
2021-09-14 06:35 Andrew Rambaut open

501D is interesting as it is in RaTG13 (i.e., one of the residues SC2 ancestors lost)

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