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These are hours of strong apprehension in Europe for the new variant of Sars-Cov-2 that emerged in England: Italy, Holland, Germany, France, Belgium and Austria have already blocked flights departing from the United Kingdom, and other countries are preparing to limit arrivals from abroad. The British government has imposed new stricter restrictions in several areas of the country, including London and the south-east of England, that is, the regions where the mutated variant has become predominant: according to British Health Minister Matt Hancock, the La variant called VUI-202012/01 or lineage B.1.1.7 is more contagious than 70% and can increase the Rt index by 0.4%. But what are the mutations that make this most effective in terms of transmission?
Mutations of the new variant of Sars-Cov-2
The new variant, first identified on September 20, 2020 in Kent, the county southeast of London, and on September 21 in the capital, is characterized by “a higher than usual number of genetic changes in the virus“Explain the researchers of the Covid-19 Genomics Consortium (CoG-UK), the organization that includes the main British universities, in the study in prepress which describes the genomic sequence of the new variant. In detail, compared to previous variants observed since the start of the pandemic (D614G that appeared in Italy between February and March, 20A.EU.1 that emerged in northeast Spain, and the Y453 strain identified on some farms mink in Denmark) changes in the new lineage B.1.1.7 include a unique combination of specific mutations and deletions, totaling seventeen, eight of which involve the Spike protein that the virus uses to bind to the ACE2 receptor on human cells and penetrate them.
The list of 17 mutations of B.1.1.7
Gene / nucleotide / amino acid
ORF1ab / C3267T / T1001I
ORF1ab / C5388A / A1708D
ORF1ab / T6954C / I2230T
ORF1ab / 11288-11296 deletion / SGF deletion 3675-3677
Peak / 21765-21770 deletion / deletion HV 69-70
Peak / 21991-21993 deletion / deletion Y144
Peak / A23063T / N501Y
Peak / C23271A / A570D
Peak / C23604A / P681H
Peak / C23709T / T716I
Peak / T24506G / S982A
Peak / G24914C / D1118H
Orf8 / C27972T / Q27stop
Orf8 / G28048T / R52I
Orf8 / A28111G / Y73C
north / 28280 GAT-> CTA / D3L
north / C28977T / S235F / small>
Effects already known and yet to be determined
As mentioned, most mutations fall in the viral RNA regions that they encode. for the protein Spike and, based on the evaluation of its effect on the structure and function of the virus, the most relevant appears to be N501Y (in orange in the figure) that affect key residues at the cellular ACE2 receptor binding site. “Experimental data – indicate scholars – suggest that the N501Y may increase affinity for the ACE2 receptor”.
Deletions (in light blue) affecting regions known to be recognized also contribute to potential surface variation of the Spike protein. of some neutralizing antibodies. However, the effect of the other mutations (in blue) is less clear. “The N501Y mutation – the scholars point out – has also been associated with an increase in infectivity and virulence in a mouse model“Regarding the elimination of two amino acids at sites 69-70, the researchers indicate that this is one of the most recurrent changes in the N-terminal domain of the viral protein, observed in multiple variants, including that associated with the mink in Denmark.
Outside of Spike, the mutation Orf8 Q27stop “truncates the Orf8 protein or renders it inactive, allowing the accumulation of subsequent mutations“In particular, this mutation has been observed in other isolated variants, including the one identified in Singapore for which it was found that”has only a very modest effect on virus replication in primary cells of the human respiratory tract compared to viruses without clearance, leading to a slight delay in replication compared to viruses with clearance“Also, since the Orf8 protein is usually made up of 121 amino acids,”it is likely that the stop codon at position 27 observed in variant B.1.1.7 cause a loss of functionAnd probably a lower severity of the disease.
In general, the researchers indicate, the overall functional effect of this series of mutations not yet determined, but “Given the plausible and experimentally predicted phenotypic consequences of some of these mutations, their unknown effects when present in combination, and the high growth rate of this new variant in the UK, the B.1.1.7 lineage requires urgent laboratory characterization. and improved genomic surveillance around the world”.
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