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Slack / Private Message Drop, pp.332-333 [SLACK_000546] · slack_pm:msg:03499

Date: 2020-12-21 13:06
Type: chat message · slack
recipient: Kristian G. Andersen, Edward C. Holmes, Andrew Rambaut
speaker: Robert F. Garry
Topics: Furin cleavage site and molecular features Therapeutics and treatments

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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]

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2020-12-21 13:06 Robert F. Garry

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]
2020-12-21 13:10 Edward C. Holmes open

What was the Nigeria post?
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.
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:
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.

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