Slack / Private Message Drop — page 333

[Robert 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 et al. 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 13:10:45] [Eddie Holmes] What was the Nigeria post? [2020-12-21 13:15:42] [Robert 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. In human 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 than Thr487. 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 up too well. [2020-12-21 13:49:41] [Robert Garry] 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 in mice." Will Alina, Relman Ebright jump on the bandwagon?:exploding_head: [2020-12-21 13:52:04] [Andrew Rambaut] 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. [2020-12-21 13:52:22] [Eddie Holmes] SO3 [2020-12-21 13:52:32] [Andrew Rambaut] We even considered it for a bit [2020-12-21 13:54:25] [Eddie Holmes] Porton Down does have that bad rap after all [2020-12-21 13:54:29] [Andrew Rambaut] 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). [2020-12-21 13:56:37] [Eddie Holmes]