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Slack / Private Message Drop, p.996 [SLACK_001210] · slack_pm:msg:10392

Page text: p.996 · original PDF

Date
2021-09-14 06:34
Type
chat message · slack
recipient
Kristian G. Andersen, Robert F. Garry, Edward C. Holmes
speaker
Andrew Rambaut
Topics
Natural origin / zoonotic spillover

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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```

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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``` own voice, substantive speaker_own asserts

In context

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  1. 2021-09-14 06:23 Andrew Rambaut open
    (i.e., a Delta)
  2. 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.
  3. 2021-09-14 06:27 Robert F. Garry open
    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.
  4. 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.
  5. 2021-09-14 06:34 Andrew Rambaut
    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```
  6. 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?
  7. 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)
  8. 2021-09-14 06:36 Robert F. Garry open
    For completeness - here's P681R - as discussed previously it changes one of the O-linked glycans [shared file(s): image.png]
  9. 2021-09-14 06:36 Andrew Rambaut open
    The loss of furin cleavage and some RBD mutations seems like it might be non-human

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