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Slack / Private Message Drop, p.339 [SLACK_000553] · slack_pm:msg:03569

Date: 2020-12-22 12:32
Type: chat message · slack
recipient: Kristian G. Andersen, Edward C. Holmes, Andrew Rambaut
speaker: Robert F. Garry
Topics: Furin cleavage site and molecular features

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Compiling some of the RBD mutations in the mice, minks and humans and comparing to the "contact" residues in ACE2 of the three species. I need to double-check that I have all the mutations -there is also some disagreement ormaybe it's just confusion I need to resolve on my part on the contact residues. For example: N501Y/T could interact with Y41 or K/H353 or both. Does not seem likely that the species adaptations falling onto the analogous residues isby chance, particularly when you superimpose the SARS1 civet to human story detailed in the JVI paper above. Bottom line is most but not all of the mutations are in residues that contact ACE2 and all are likely in epitopes, most but maybe not all neutralizing.

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2020-12-22 12:32 Robert F. Garry

Compiling some of the RBD mutations in the mice, minks and humans and comparing to the "contact" residues in ACE2 of the three species. I need to double-check that I have all the mutations -there is also some disagreement ormaybe it's just confusion I need to resolve on my part on the contact residues. For example: N501Y/T could interact with Y41 or K/H353 or both. Does not seem likely that the species adaptations falling onto the analogous residues isby chance, particularly when you superimpose the SARS1 civet to human story detailed in the JVI paper above. Bottom line is most but not all of the mutations are in residues that contact ACE2 and all are likely in epitopes, most but maybe not all neutralizing.
2020-12-22 12:39 Robert F. Garry open

@Kristian Andersen I think that the P681H mutation potentially could also be "fitness enhancing" for the reasons discussed above. I'm thinking that E417N, E484K and perhaps S494P (but proline) are probably pure immune escape.
2020-12-22 12:43 Kristian G. Andersen open

@Kristian Andersen But how the heck does the SA lineage get its 'transmission' phenotype then? If it has it, thatis... It's N501Y, E484K, N417K

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