Authors: Alessandro Vitale, Barbara Illi, Duccio Cavalieri.

These days a variant of the virus known as SARS-CoV-2 is spreading rapidly throughout Europe, this variant first isolated from a British patient raises important questions that we try to answer:

What is the English variant?
The new variant, christened “B.1.1.7,” has, compared to the original Wuhan strain, 17 mutations that change or remove amino acids, in four different proteins of the virus. Eight mutations are in the Spike protein, the very one against which BioNtech-Pfizer’s Moderna and Astra Zeneca vaccines were developed. The concrete effect of each of the mutations is currently unknown, but based on preliminary analyses three of them could alter infectious capacity: the first, N501Y could make it easier for the virus to bind to the gateway it uses to enter our cells, the ACE2 receptor; the second, deletion 69-70, could make molecular diagnosis (swabs) more complicated; and the third, P681H, could alter a site with a crucial role in infection.

But has the virus mutated?
That the virus is rapidly evolving, however, is not surprising. A mutation is an error randomly inserted when the virus duplicates. The greater the number of patients, the more mutations the virus accumulates and selects to be transmitted.

RNA viruses mutate more than DNA viruses, but the presence of a kind of eraser-the so-called “proofreader”-in the genome of coronaviruses had suggested the introduction of few errors. Therefore, the public was often told that “the virus has not mutated.” However, sequence analyses carried out during the first wave of the infection revealed thousands of mutations that emerged independently.

At least 8 of these mutations spread with a frequency that cannot be explained by chance, so they were selected during the evolution of the virus. Spike is one of the genes that mutates the most, especially in the region that binds ACE2, the “gateway” that allows the virus to enter our cells. This is expected, since a virus that has an interest in propagating itself adopts better and better “docking” strategies to its host.

For example, the mutation prevalent in Italy, called D614G, and which emerged in Lombardy in March 2020, is associated with higher viral loads than those observed in the ancestral strain. However, we have known for several weeks that this variant, which is now the prevalent one in Italy, had not reached its potential spread limit. And now here is news of the new English variant.

Nothing in biology can be understood except in the light of evolution, and even for the COVID-19 pandemic, evolutionary biology models predicted an evolution of the virus to a more transmissible but no longer lethal form.


Is the UK variant more dangerous than the others?
What is of concern about this variant are three elements: that it may become more diffusible; that it may be more harmful to health; and that it may be insensitive to vaccines.
In the UK, this variant is increasing rapidly in percentage compared to all other variants, strongly suggesting that it is more diffusible.
Apparently it is not more harmful to health. It is definitely important to know that one of the predictions is that the lethality of the virus should slowly decrease, increasing the fraction of carriers with mild symptoms, this is because a virus is a parasite and one so contagious has no interest in killing its host. This does not mean that more harmful variants do not arise, but it is to be expected that they will disappear after a not-so-long time, because by severely and quickly damaging the host they make their transmission less likely.


What about vaccines?
Based on what we know today it can be argued that vaccines will work. Vaccines in production generate antibodies against different portions of the Spike protein. Each existing protein has its own characteristic three-dimensional shape that allows it to function optimally and exposes certain sites on the surface that can stimulate antibody production. Precisely because there are so many Spike sites that are “seen” by antibodies, it is unlikely that single mutations, in different portions, would impair antibody binding to the virus.

Should we be concerned?
In conclusion, it is right to follow the evolution of this variant carefully because the transmission rate has probably increased. But one should not be overly alarmed. At the moment there is no evidence that it causes greater health damage or can compromise the efficacy of recently approved vaccines. Certainly it is essential to build a monitoring system that not only tells us if you are positive, but also which variant and how it is spreading, acquiring essential information about the evolutionary dynamics of the pandemic.


For further discussion:
– COG-UK update on SARS-CoV-2 Spike mutations of special interest. Report 1. Prepared by COG-UK, December 19th, 2020
– Covid-19: New coronavirus variant is identified in UK. News Briefing.
BMJ2020;371:m4857. http://dx.doi.org/10.1136/bmj.m4857. Published: 16
December 2020
– European Centre for Disease Prevention and Control. Rapid increase of a SARS-CoV-2 variant with multiple spike protein mutations observed in the United Kingdom – December 20, 2020. ECDC: Stockholm; 2020.