1/ All eyes are on England because of the #B117 variant (501Y.V1/VOC202012/01).

But WHY could the variant #B1351 (501Y.V2) detected in South Africa pose a bigger danger?

To better understand this, let's go back to summer and take a seat for an experimental time travel in Siena: https://twitter.com/ncholia/status/1345819541989969923

2/ The -immunology group of Rappuoli used the serum of 20 post- #COVID19 patients, whose polyclonal antibodies were well bound to the Spike-protein at a borderline concentration, so as not to destroy #SARSCoV2 but allowed them to replicate in a cell culture with presence of pAbs

3/ This was done using so-called passages. So this experiment was repeated over and over and after a whole number of repetitions, after seven passages, 45 days later, there was a first difference, a deletion of an amino acid at position 140 on the S-NTD:
https://www.biorxiv.org/content/10.1101/2020.12.28.424451v1

4/ ΔF140. Fine. Twelve passages later, the virus is suddenly able to replicate better than in the previous passages. On day 80 of the experiment, on the S-RBD, an important mutation occurred: E484K
Amino acids Glutamate and Lysine has been replaced at 484th position on the RBD.

5/ This mutation, which occurred spontaneously under experimental in-vitro conditions, is present by #B1351 that occurs in South Africa under natural conditions! We know that this can cause immune evasion by an escape mutation. The virus can gain the ability to escape from Abs. https://twitter.com/jbloom_lab/status/1346442016092082176

6/ The final mutation occurred in 14th pas. An insertion of 11 AAs into: Y248-L249, flexible loop region.

There is also a glycosylation point in it, these junctions are designed to keep Abs from binding. When this virus acquired this mutation, it was then insensitive to the ABs.

7/ But at a very close place like this, that is the position in the -experiment position 248, at position 246, only two AAs away, the #B1351 has an AA-substitution: R246I

In addition, #B1351 has another mutations on the RBD:

K417N & N501Y #B117
https://www.medrxiv.org/content/10.1101/2020.12.21.20248640v1

8/ Taken together, this suggests that something has changed quite a bit on the RBD. Maybe even stronger than #B117. Before August, estimated, 34-41% of the population was infected with the virus in major cities of many African countries, including Kenya.
https://www.medrxiv.org/content/10.1101/2020.09.02.20186817v1

9/ The E484K escape mutation may have been caused by immunosuppression, which has evolved against the virus: Natural selection.

We see exactly the same mutation in a variant that originated in a country where we know that there is already something like background immunity in SA

10/ which is remarkable. You have to take that seriously.

Perhaps we may be facing here a bigger problem than the 501.V1.

A lot of people traveled to South Africa over the christmas & new year. It is a popular Christmas travel destination in the southern hemisphere.

11/There are still tourists coming back from South Africa these days. That's why

501.V2 should be taken as SERIOUSLY,

countries should IMMEDIATELY sequence for 501.V2 too,

results should be entered into global databases [ @nextstrain],

all measures should be increased!

https://twitter.com/ncholia/status/1346926681546764291