Worrying Multiple Spike Protein Mutations Observed in the New SARS-Cov-2 UK Strain

In the United Kingdom, a new strain of the SARS-Cov-2 coronavirus has been spreading rapidly since December, leading many countries to close their borders to UK citizens. The variant, called VUI 202012/01, was first identified on 20 and 21 September 2020 in Kent and Greater London, respectively. At that time, it represented only a small proportion of SARS-Cov-2 infections. In the following months, it was responsible for an increasing number of infections and spread to other regions. On 13 December 2020, 1,108 people were infected with variant VUI 202012/01, mainly in Kent and London, but also in Scotland, Wales, and 4 other foreign countries.

SARS Cov-2

The European Center for Disease Prevention and Control (ECDC) is closely monitoring the situation. Based on the work of the Covid-19 Genomics Consortium UK (CoG-UK), the ECDC published in a report on the 20th of December what is known about the new strain.

Numerous mutations in the Spike protein

Table of Contents

1 Numerous mutations in the Spike protein
2 Is the new variant more dangerous?
3 Effects on vaccines
- - 3.0.1 References

Variant VUI 202012/01 is characterized by a large number of S protein mutations throughout the genome. Therefore, it is placed in a phylogenetic cluster (called lineage B.1.1.7). B.1.1.7 is characterized by 14 non-synonymous mutations, 3 deletions, and 6 synonymous mutations, for a total of 23 genetic alterations. In comparison, the other variants of SARS-Cov-2, grouped in the same phylogenetic cluster, share only a handful of Spike protein mutations.

Among the deletions and non-synonymous mutations are several in the S protein. It is the key that opens the door for the entry of the virus into the host cells, and any change in it has potentially important implications for the biology of the virus.

Variant VUI 202012/01 has a tyrosine instead of asparagine at position 501 (mutation N501Y). The amino acid at position 501 of the S protein is located in the nucleus of the receptor-binding domain (RBD), the region in direct contact with the ACE2 receptor. According to the report of the CoG-UK scientists, it was observed in experiments with mice that such modification increases the affinity of the S protein for ACE2.

A second mutation is in another important part of the S protein. A histidine replaces a proline in position 681 (P681H mutation). This residue is one of the four that form the catalytic site for furin (an enzyme that cleaves proteins in a specific sequence of amino acids). It catalyzes one of the two stages of S protein maturation necessary for the fusion between the viral and cellular membranes.

The N501Y and P681H mutations were observed separately in other strains, but VUI 202012/01 has both, which has never been documented. The final mutation in the S protein that scientists are interested in is a deletion (the complete loss of a nucleotide) in the N-terminal part of the spike

Is the new variant more dangerous?

In its report, the ECDC discusses the potential impact of mutations in VUI 202012/01 on human health. First of all, it should be kept in mind that viruses transform every time they reproduce. These mutations are not always corrected and can therefore spread. Most mutations do not alter the biology of the virus and its presence should not be a cause for concern. Mutations are a normal biological process.

However, certain mutations give the virus advantages. In the case of VUI 202012/01, information is still limited, but it is possible that the mutations have increased the transmissibility of the virus. The R0 of VUI 202012/01 could be 0.4 times higher according to the modeling of the Nervtag (The New and Emerging Respiratory Virus Threats Advisory Group). At the moment, there is no evidence that the virus is more deadly and causes more severe forms of Covid-19. It should be noted that this variant has been isolated primarily in young people under 60 years of age, who are less likely to develop severe forms.

Effects on vaccines

In terms of the diagnosis, the new variant may escape some RT-PCR tests because of the suppression present in the N-terminal portion. Some PCRs specifically look for the S protein gene to diagnose infection, among other WHO-recommended genes. The number of infections caused by VUI 202012/01 might then be underestimated.

Finally, there is the question of the efficacy of the Pfizer-BioNTech vaccine currently being administered in several countries: will the antibodies resulting from the vaccination be able to recognize the modified S protein of VUI 202012/01? Currently, there are no data to answer this question, but according to the ECDC, tests are being conducted to characterize the specific antigens of the new variant. Pfizer-BioNTech is already testing the efficacy of its vaccine in the new variant. The messenger RNA technology allows the pharmaceutical company to adapt its vaccine in as little as six weeks, Ugur Sahin, co-director of BioNTech said Dec. 22.