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Slack / Private Message Drop, p.338 [SLACK_000552] · slack_pm:msg:03561

Page text: p.338 · original PDF

Date
2020-12-22 08:11
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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https://jvi.asm.org/content/82/14/6984 Relevant paper: "They show that the major species barriers are determinedby interactions between four ACE2 residues (residues 31, 35, 38, and 353) and two RBD residues (residues 479and 487), that early civet SARS-CoV isolates were prevented from infecting human cells due to imbalanced saltbridges at the hydrophobic virus/receptor interface, and that SARS-CoV has evolved to gain sustained infectivity for human cells by eliminating unfavorable free charges at the interface through stepwise mutations at positions 479and 487."

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https://jvi.asm.org/content/82/14/6984 Relevant paper: "They show that the major species barriers are determinedby interactions between four ACE2 residues (residues 31, 35, 38, and 353) and two RBD residues (residues 479and 487), that early civet SARS-CoV isolates were prevented from infecting human cells due to imbalanced saltbridges at the hydrophobic virus/receptor interface, and that SARS-CoV has evolved to gain sustained infectivity for human cells by eliminating unfavorable free charges at the interface through stepwise mutations at positions 479and 487." quoted / not their view quoted_external sentence carries quotation marks asserts

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  1. 2020-12-22 07:29 Robert F. Garry open
    From Sun - Fig S8 Shows that N501Y comes up quick followed by Q493H. then K417N. [shared file(s): image.png]
  2. 2020-12-22 07:40 Kristian G. Andersen open
    Probably more 'immune' related than 'mouse' related?
  3. 2020-12-22 07:48 Robert F. Garry open
    Yeah - the fact these are epitopes to me strongly suggests immune selection - mouse or human. But I think that the particular substitution may depend on the species. Analysis coming...:sunglasses:
  4. 2020-12-22 08:11 Robert F. Garry
    https://jvi.asm.org/content/82/14/6984 Relevant paper: "They show that the major species barriers are determinedby interactions between four ACE2 residues (residues 31, 35, 38, and 353) and two RBD residues (residues 479and 487), that early civet SARS-CoV isolates were prevented from infecting human cells due to imbalanced saltbridges at the hydrophobic virus/receptor interface, and that SARS-CoV has evolved to gain sustained infectivity for human cells by eliminating unfavorable free charges at the interface through stepwise mutations at positions 479and 487."
  5. 2020-12-22 08:28 Robert F. Garry open
    The equivalent amino acids to SC1 479 and 487 in terms of alignment to RBD appear to me to be 493 and 501, but Ineed to really take a closer look at ALL the structures.
  6. 2020-12-22 08:52 Robert F. Garry open
    Those are the same and it's the alignment in PO1.
  7. 2020-12-22 08:54 Robert F. Garry open
    SC1 479 and SC2 493 interact with ACE2 similarly - however SC1 487 and SC2 501 interactions with ACE2 are completely different... *Correction - not completely different - just different*
  8. 2020-12-22 09:21 Robert F. Garry open
    The pattern of prolines in SC1 and SC2 RBDs are distinct - look at PO1 - which creates a very different interaction with ACE2 - but we're seeing in real time the adaptation of SC2 to receptors in humans, minks and mice pretty muchas you'd draw it up. The twist that it may be immune selection driving better receptor binding is not expected at leastby me. Tuning up receptor binding affinity happened in SARS1 per the JVI paper above, but more subtle and [probably?] not an immune component there in 2002 and 2005.

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