Prediciting Viral Evolution31 Jan 2021 15:09
Yesterday Jeremy Farrar tweeted a paper
https://twitter.com/JeremyFarrar/status/1355601609372430336
https://www.biorxiv.org/content/10.1101/2021.01.06.425392v3
Its a complex read but pretty brilliant paper.
Basically in the lab they have experimented with virus evolution. In vitro evolution can mimic natural evolution, on a much faster time scale so we can predict what likely mutations will occur next.
Predicted Q498R mutation
Q498R was first observed in library B4, but established itself only in B5. This mutation emerges only together with N501Y, suggesting an epistatic effect between the two mutations. Indeed, deep-mutational scanning of single RBD mutations 6 showed Q498R to negatively affect both protein stability and binding, while we show that in combination with N501Y binding affinity is improved by ~4-fold above N501Y alone.
Rapid spread of N501Y in the population increases the likelihood for the emergence of the Q498R mutant, which will probably have even higher infectivity. Conversely to Q498R, both the N501Y and E484K mutations established themselves independently, allowing for their rapid in vitro selection and emergence in SARS-CoV-2. This suggests that with the spread of the “British”, “Brazilian”, and “South African” variants, we project that the Q498R mutation will appear in the future, on top of these mutations. The synergism of Q498R with N501Y and E484K increases ACE2 binding by ~50-fold relative to WT.
4 to 50 fold increase in infectivity thats bad!
However the good news is for vaccine/drug designs we get a heads up of how the virus will likely mutate in the future. In theory we could develop vaccine boosters in preperation for when this likely mutation occurs.
Download the pdf and read the discussion and conclusion section as gives you a good idea of whats coming next. Interesting that cloth face masks won't cut it and everyone will need N95 masks in the near future.
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