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Slack / Private Message Drop, p.333 [SLACK_000547] · slack_pm:msg:03505

Page text: p.333 · original PDF

Date
2020-12-21 13:52
Type
chat message · slack
recipient
Kristian G. Andersen, Robert F. Garry, Edward C. Holmes
speaker
Andrew Rambaut

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We even considered it for a bit

In context

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  1. 2020-12-21 13:15 Robert F. Garry open
    Just to revisit Baric https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7081895/ "Second, residue 501 in 2019-nCoV RBD (corresponding to residue 487 in SARS-CoV) is an asparagine. Based on our previous structural analysis, residue 487 in SARS-CoV is located near virus-binding hot spot Lys353 (i.e., hot spot 353) on human ACE2 Fig.1C. Hot spot 353 consists of a salt bridge between Lys353 and Asp38 also buried in a hydrophobic environment. In civet SARS-CoV RBD (year 2002), residue 487 is a serine, which cannot provide favorable support for hot spot 353. Inhuman SARS-CoV isolated in year 2002, residue 487 is a threonine, which strengthens the structural stability of hot spot 353. The S487T mutation adds the favorable interaction at the RBD-human ACE2 interface, enhances viral binding to human ACE2, and plays a critical role in the human-to-human transmission of SARS-CoV. In human SARS-CoV isolated in year 2003, residue 487 is a serine and there was no human-to-human transmission for this SARS-CoV strain. Asn501 in 2019-nCoV RBD provides more support to hot spot 353 than Ser487 but less thanThr487. This analysis suggests that 2019-nCoV recognizes human ACE2 less efficiently than human SARS-CoV (year 2002) but more efficiently than human SARS-CoV (year 2003). Hence, at least when considering the ACE2-RBD interactions, 2019-nCoV has gained some capability to transmit from human to human." It's not held uptoo well.
  2. 2020-12-21 13:49 Robert F. Garry open
    Next up: the DRASTIC krewe advances their theory that the UK variant is a lab escape. Don't bother, but this from one of the DRASTIC stars: "Both the S1, the RBM and the FCS of the UK variant show obvious sign of adaptation inmice." Will Alina, Relman Ebright jump on the bandwagon?:exploding_head:
  3. 2020-12-21 13:52 Andrew Rambaut open
    It is a way more likely hypothesis than the Wuhan lab in that there is provably SARS-CoV-2 in hundreds of labs doing a thousand different experiments.
  4. 2020-12-21 13:52 Edward C. Holmes open
    SO3
  5. 2020-12-21 13:52 Andrew Rambaut
    We even considered it for a bit
  6. 2020-12-21 13:54 Edward C. Holmes open
    Porton Down does have that bad rap after all
  7. 2020-12-21 13:54 Andrew Rambaut open
    But given the South African outbreak has a very similar pattern I am still going for chronic immunocompromised human (and there are obviously lots in South Africa).
  8. 2020-12-21 13:56 Edward C. Holmes open
    Totally agree. Might be good if DRASTIC were distracted for a while.
  9. 2020-12-21 14:04 Kristian G. Andersen open
    Chronic infection seems more likely to me - however, I don't think we can rule out potential epizootic spilling back into humans. But all these mutations certainly look consistent with chronic infection

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