Slack / Private Message Drop — page 338

[Eddie Holmes] https://www.krisp.org.za/publications.php?pubid=315 [2020-12-22 01:50:54] [Andrew Rambaut] Yeah. Was on a call list night with Tulio. They don't really have any epi that it is spreading faster but it is spreading very fast. [2020-12-22 05:54:06] [Robert Garry] The development of monoclonal antibody resistant mutants (MARMs) is an important clue that immune escape might be driving the emergence of the various Nellys and the elephant. K417, E484 and Q493 make the list of MARMs to various Regeneron MAbs (see Table 2). The presence of Q493K on the list of MARMs suggests that in the Baric and Sun mouse passage experiments immune section could have played a role in the emergence of the mouse pathogenic variant. https://science.sciencemag.org/content/369/6506/1014 [2020-12-22 06:10:51] [Robert Garry] Just noting that Q493K made the list of mutations discussed in channel above in the NEJM immunosuppressed patient who got the Regeneron MAbs. [2020-12-22 07:29:48] [Robert Garry] From Sun - Fig S8 Shows that N501Y comes up quick followed by Q493H. then K417N. [shared file(s): image.png] [2020-12-22 07:40:53] [Kristian Andersen] Probably more 'immune' related than 'mouse' related? [2020-12-22 07:48:13] [Robert Garry] 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: [2020-12-22 08:11:37] [Robert Garry] https://jvi.asm.org/content/82/14/6984 Relevant paper: "They show that the major species barriers are determined by interactions between four ACE2 residues (residues 31, 35, 38, and 353) and two RBD residues (residues 479 and 487), that early civet SARS-CoV isolates were prevented from infecting human cells due to imbalanced salt bridges 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 479 and 487." [2020-12-22 08:28:27] [Robert Garry] The equivalent amino acids to SC1 479 and 487 in terms of alignment to RBD appear to me to be 493 and 501, but I need to really take a closer look at ALL the structures. [2020-12-22 08:52:09] [Robert Garry] Those are the same and it's the alignment in PO1. [2020-12-22 08:54:51] [Robert Garry] 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*