Thread by @firefoxx66

As far as I know, the #SARSCoV2 variant identified by Hancock today is defined by a spike mutation at position 501 N->Y & a double-deletion at positions 69/70.

You can see it in orange in the dedicated Neher Lab S:N501 @nextstrain build below
nextstrain.org/groups/neherla…

1/N

https://twitter.com/firefoxx66/status/1338523173365686275

I do not have more information about why scientists in the UK believe this variant may have increased transmission.
However, it does appear the proportion of UK sequences containing S:N501 mutations has increased recently (sorry, hard to see)

github.com/emmahodcroft/c…

2/N

This build is from last week (I'll try to update soon), but from this information, it seems like this particular variant has so far only been detected in the UK and Denmark. However, we may simply not have samples from other countries.

nextstrain.org/groups/neherla…

3/N

What do we know about S:501 mutations?

S:N501Y may increase ACE2 receptor binding (work from @jbloom_lab). It is hard to extrapolate what impact that may or may not have on actual transmission or infection.
jbloomlab.github.io/SARS-CoV-2-RBD…

4/N

S:N501 mutations have occurred multiple times in the tree, in many locations. See the dedicated S:N501 build here: nextstrain.org/groups/neherla…

5/N

@CovidGenomicsUK will release more information on this mutation today, and I really strongly recommend listening out for more concrete information from them. It is through their hard work this variant has been studied so quickly.

6/N

For information, I spoke to someone at COG-UK before sending these tweets, to check it was ok to say this mutation is the one mentioned today. Many of us are tracking variants in Europe right now, but COG-UK has been hard at work on this predominantly UK one.

7/N

As with other mutations: it is unlikely that a few mutations render a vaccine ineffective. The vaccines under development induce antibodies to many sites on Spike, so even if one target doesn't work, others should. Still, important to investigate, as scientists are doing.

8/N

@CovidGenomicsUK has released some information about the new variant identified, confirming it contains S:N501Y.

Importantly: "Efforts are under way to confirm whether or not any of these mutations are contributing to increased transmission."

9/N

cogconsortium.uk/news_item/upda…

An updated figure of the proportion of sequences from the UK in different variants, with data available through this morning - just run.

Colours still hard to see (sorry), but can see recent expansion of S:N501 variant.

10/N

Updated phylogenetic runs are "in the oven" and I'll update tomorrow with more links when I can - it's late here, and it's been a crazy evening.

Apologies in advance for my bleary eyes if you'll be hearing me talk tomorrow morning! 🙃😆

11/N

A great thread by @GuptaR_lab on 69/70 deletions more generally, and the N501Y mutation variant highlighted today:

12/N

https://twitter.com/GuptaR_lab/status/1338610098663526402

A bit confused about what all this is about? Why does the virus mutate - what even is a mutation? When should I worry?

This great thread breaks it down step-by-step and outlines more of what we know - have a read.

https://twitter.com/ewanbirney/status/1338616959437598720

13/N

We maintain a dedicated build covering sequences with mutations at spike position 501 - like the one associated with the #newvariant identified yesterday.

You can read about a new effort to track this & other variants here!

https://twitter.com/firefoxx66/status/1338792620814905345

14/N

Using the latest sequences from yesterday, we've updated a build for S:N501 - you can check it out here (the UK variant is at the top, green).

Importantly this doesn't include the latest sequences from yesterday: that's in preparation right now :)

15/N

nextstrain.org/groups/neherla…

What else do we know about mutations at S:501 more generally? The website has links to papers discussing what researchers have found out about mutations at this position. It may
- Be associated with rodent/mustelid adaptation
- Increase ACE2 binding

16/N

github.com/emmahodcroft/c…

Important to note that as far as I'm aware, there's no association with animals in the UK new variant.

Also critical to clarify that 'increased binding' may not have an impact on infection/transmission: if you can bind well enough, 'better' may not be advantageous.

17/N

We can see that 501 mutations have arisen multiple times in multiple countries, from the dedicated @nextstrain S:N501 build. Mutations changing the amino acid from N to T, Y, and S are present.

We can take a look at some of these.

18/N

The large blue circles here are samples from Australia over the summer that carry the S:N501Y mutation. This variant seems to have died out - we don't see any samples after July.

19/N