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Slack / Private Message Drop, p.333 [SLACK_000547] · slack_pm:msg:03501

Page text: p.333 · original PDF

Date
2020-12-21 13:15
Type
chat message · slack
recipient
Kristian G. Andersen, Edward C. Holmes, Andrew Rambaut
speaker
Robert F. Garry
Topics
Furin cleavage site and molecular features

Recipients on this medium are inferred from channel membership, not per-message addressing.

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.

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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. own voice, substantive speaker_own asserts
In civet SARS-CoV RBD (year 2002), residue 487 is a serine, which cannot provide favorable support for hot spot 353. quoted / not their view quoted_external inside quotation marks asserts
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. quoted / not their view quoted_external inside quotation marks asserts

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  1. 2020-12-21 13:06 Robert F. Garry open
    The Starr ref from Andrew's *brilliant* virological post [destined to be in the top 2 or 3 in importance] has this figure.As noted therein N501Y one of *very* few including the mink N501T that increase ACE2 binding. Kudos to Starr etal. who also picked up Y453F (a mink mutation that appears to be another monoclonal antibody resistant mutation)as a change that enhances ACE2 binding. [shared file(s): image.png]
  2. 2020-12-21 13:10 Edward C. Holmes open
    What was the Nigeria post?
  3. 2020-12-21 13:15 Robert F. Garry
    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.
  4. 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:
  5. 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.
  6. 2020-12-21 13:52 Edward C. Holmes open
    SO3
  7. 2020-12-21 13:52 Andrew Rambaut open
    We even considered it for a bit

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