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Slack / Private Message Drop, pp.734-735 [SLACK_000948] · slack_pm:msg:07686

Date: 2021-04-28 07:00
Type: chat message · slack
recipient: Kristian G. Andersen, Edward C. Holmes, Andrew Rambaut
speaker: Robert F. Garry

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```1 msdngpqnqr napritfggp sdstgsnqng ersgarskqr rpqglpnnta swftaltqhg 61 kedlkfprgq gvpintnssp ddqigyyrra trrirggdgk mkdlsprwyf yylgtgpeag 121 lpygankygi iwvategaln tpkdhigtrn pannaaivlq lpqgttlpkg fyaegsrggs 181 qassrsssrs rnssrnstpg ssRGTsparm agnggdaala lllldrlnql eskisgkgqq 241 qqgqtvtkks aaeaskkprq krtatkaynv tqafgrrgpe qtqgnfgdqe lirqgtdykh 301 wpqiaqfaps asaffgmsri gmevtpsgtw ltytgaikld dkdpnfkdqv illnkhiday 361 ktfpptepkk dkkkkadetq alpqrqkkqq tvtllpaadl ddfskqlqqs mssadstqa``` Nucleocapsid sequence. Like Lassa N and several other RNA virus nucleoproteins there is a 2-domain structure. The N-term domain binds RNA. The C-term domain mediates dimerization. In btwn the two domains is a linker. In SC2 the linker is arginine serine (RS) rich. It is "intrinsically disordered" and therefore does not show up in the X-rayor cryo structures. 203-205 sequence RGT is near the end of the linker. The linker is highly phosphorylated -therefore probably regulates N function - the mutations could impact those functions which could affect assembly, virus load or virus distribution etc and yes this will impact transmissibility.

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2021-04-28 06:55 Andrew Rambaut open

'neglected' - https://twitter.com/angie_rasmussen/status/1387397186372005893
2021-04-28 06:55 Andrew Rambaut open

Perhaps Sputnik V will just spread round the world of its own accord?
2021-04-28 06:56 Kristian G. Andersen open

Wait, what????
2021-04-28 07:00 Kristian G. Andersen open

@Andrew Rambaut - here's the B.1 lineage. A few in the US: https://outbreak.info/situation-reports?pango=B.1&am p;muts=S%3AN501Y&muts=S%3AE484K&mut[...]AR346K&muts=S%3AP681H&loc=USA&am p;loc=USA_US-CA&selected=Worldwide
2021-04-28 07:00 Robert F. Garry

```1 msdngpqnqr napritfggp sdstgsnqng ersgarskqr rpqglpnnta swftaltqhg 61 kedlkfprgq gvpintnssp ddqigyyrra trrirggdgk mkdlsprwyf yylgtgpeag 121 lpygankygi iwvategaln tpkdhigtrn pannaaivlq lpqgttlpkg fyaegsrggs 181 qassrsssrs rnssrnstpg ssRGTsparm agnggdaala lllldrlnql eskisgkgqq 241 qqgqtvtkks aaeaskkprq krtatkaynv tqafgrrgpe qtqgnfgdqe lirqgtdykh 301 wpqiaqfaps asaffgmsri gmevtpsgtw ltytgaikld dkdpnfkdqv illnkhiday 361 ktfpptepkk dkkkkadetq alpqrqkkqq tvtllpaadl ddfskqlqqs mssadstqa``` Nucleocapsid sequence. Like Lassa N and several other RNA virus nucleoproteins there is a 2-domain structure. The N-term domain binds RNA. The C-term domain mediates dimerization. In btwn the two domains is a linker. In SC2 the linker is arginine serine (RS) rich. It is "intrinsically disordered" and therefore does not show up in the X-rayor cryo structures. 203-205 sequence RGT is near the end of the linker. The linker is highly phosphorylated -therefore probably regulates N function - the mutations could impact those functions which could affect assembly, virus load or virus distribution etc and yes this will impact transmissibility.
2021-04-28 07:01 Andrew Rambaut open

@Kristian Andersen I think this one is interesting because it has almost nothing else other than Phil and Doug from before and then the 4 spike mutations
2021-04-28 07:02 Andrew Rambaut open

@Kristian Andersen It is like a really pure constellation.
2021-04-28 07:02 Kristian G. Andersen open

@Kristian Andersen Agreed. We have started seeing a lot of B.1, so we'll be on the lookout.
2021-04-28 07:04 Kristian G. Andersen open

That Sputnik V stuff is crazy AF. I wonder if the Ad26 is competent too? Ad5 is pretty prevalent, so while certainly aproblem, less so. Ad26 on the other hand...

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