A closer look at B.1.1.7

Here let us try to take a closer look at the genome of the new lineage of SARS-CoV-2 recently identified in the Greater London Area of the United Kingdom.

According to Andrew Rambaut et al (2020), there was a number of unusual genetic changes in the new lineage (B.1.1.7), some of which were unprecedented to date. Very briefly, there were 14 mutations related to the changes in amino acid (the basic components of proteins) sequence; moreover, 3 mutations led to the deletion of certain amino acids. In total, there were 17 mutations, which were effective to cause changes in the protein structure and its biological properties.

In terms of the potential biological effects of the mutations, there are some highlights.

  1. Mutation N501Y, like D614G that we discussed before, was believed to increase the binding between the virus and its human receptor (ACE2); thus, the virus with this mutation is likely to be more infectious and deadly (at least in animal model);
  2. Mutation P681H was found at a position that could be linked to the promotion of viral entry. In other words, the new virus may enter human host cells more efficiently. In theory, people may become more susceptible to the viral infection;
  3. Furthermore, N501Y and P681H were found together in the same virus for the first time;
  4. Mutation 69-70del, causing the deletion of two amino acids at sites 69 and 70 of the viral spike protein, has been reported in other strains. This mutation might allow the new virus to escape from the host’s immunity;
  5. There were other mutations found outside the spike protein, ORF8 Q27stop mutation for example, resulted in an incomplete form of OFR8 protein. It is particularly worth noting that OFR8 protein has been reported to be involved in normal immune response;
  6. Mutations 69-70del and QRF8 Q27stop could help the virus overcome the host’s immune response.

Taken together, regarding the questions of my previous post (unfortunately, the answers of the first three appear to be discouraging), I feel a bit pessimistic for the next few months: it seems that, with reference to the available evidence, the new virus could be very difficult to contain on the one hand; it is likely to bring in more impact to the patients and the healthcare system on the other. At this point, I cautiously urge that we should refer to the ‘second wave’ of the Spanish flu for some contingency plans.

With reference to COVID-19 Genomics UK Consortium’s report dated on 19 December 2020, it described some viral strains with other mutations, such as N439K, Y453F, A222V, and so on. Mutations N439K and Y453F, in particular, could possibly be implicated to the protective effects of the vaccines against COVID-19. Scientists and physicians must keep track of all the findings for this potential threat to mankind. One of the most urgent questions to be answered is that ‘are those established treatments still effective on that new virus?’

Good luck to the UK and Denmark! Hong Kong must get prepared!

(Photo credit: Time Magazine. Photographer: Jason Alden/Bloomberg via Getty Images)

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