Mutate or die, stupid!

Viruses do not mutate because they want to do it.

It is a random phenomenon of nature.

Nucleic Acids. Image credit: NIH. National Human Genome Research Institute.

Life’s avatars live in a combination fortuitous of four letters. They are Adenine (A), Guanine (G), Cytosine ©, Thymine (T) in the DNA, and A, G, C, and Uracil (U) in the RNA. In the DNA, there is T and U in the RNA.

A virus is, as someone said, an enigma enclosed in a layer of lipids. There are thousands of species of viruses, some formed by DNA and others by RNA. By genetic mandate (written in their genomic code), RNA viruses are mutating.

A virus is, as someone said, an enigma enclosed in a layer of lipids.

Viruses are intracellular parasites. They need to enter bacteria or plant and animal cells for their survival. There they use synthetic cellular machinery to build structural proteins. Viruses lack such machinery. So, they must use the borrowed one to their advantage as real biological ‘squatters.

Viruses are like biological squatters. Image credits: PA. The Guardian.

Mutations.

A mutation is a minimal single-letter change in the genome (A by G). The mutations occur at random, and they are inherent to RNA viruses.

Most changes are harmless, harmful, or deleterious to the mutant virus. Some are adaptive mutations to spread faster, with more efficient contagion. It causes cell death and more severe disease or patients’ death. Thanks to some mutations, the virus can avoid the host’s immunity. And resist antiviral drugs’ aggression (drug resistance), and invalidate some vaccines.

A mutation is a minimal, single-letter change in the genome.

The coronavirus has a genetic text with errors.

The current pandemic virus SARS CoV-2 (‘corona’) has a genome of 30,000 letters. Corona is a mutagenic RNA virus with around two new changes every month. The evolutive phenomenon was happening in the animal world. It happened for thousands of years long before humans were the viral goal, as it happens now.

Several viral variants emerged. It happened few weeks after the beginning of the epidemic (December 2019). In China, Europe, Australia, or the USA. So far (December 2020), there are more than 100,000 viral genomes analyzed. And many corona mutations have existed. Most are of no significance to the virus or humans.

Some have jumped from research laboratories to the mass-media. The best known is mutation G614D, by a change or substitution of single amino acid. After spreading worldwide (80% of infections), it emerged in Europe (February 2020).

It shows a better transmission. Also, it has a higher viral load, at least in experimental models (Figure 1). It does not seem to be more aggressive, nor does it affect treatments or vaccines’ efficacy.

Figure 1. The panel above shows the G614 mutation appearance in February 2020. There is an increase in May-June. The bottom panel expresses the infection’s size. The figure on the right (all blue) with the G614 mutation produces more copies of the virus (viral load). Image credits: Cell, 2020: 182 (4): 812–827.

A viral variant is sweeping England and the world.

SARS CoV-2 mutates less (2–6 times) than seasonal influenza viruses. Many other mutations (over 13,000) have emerged so far, almost all inconsequential.

There is a new variant: VUI-202012/01 (Variant Under Investigation-year 2020, month 12, number 1), or lineage B.1.1.7. It is prevalent and expanding. An intriguing clue is that it presents at least 17 mutations or changes in the S (Spike) protein. One of them is N501Y, the media star of the moment.

The variant’s geographical origin is not very clear. It started in Brazil in April 2020. It surged in Kent (UK) on 20 September 2020. Now it is sweeping England, especially the south and southwest. Denmark, the Netherlands, and Australia also detected the mutation in some cases. It will spread worldwide. A similar variant, but not the same, accounts for 90% of South African patients. It can have increased transmissibility.

An intriguing clue is that it presents at least 17 mutations or changes in the S (Spike) protein. One of them is N501Y, the media star of the moment.

It seems that the ‘British’ variant also spreads fast. The explanation is that seven mutations affect the S protein. This fact allows the coronavirus to improve cell receptor (ACE2) binding to enter the cell.

SARS CoV-2 original has twenty times more affinity for ACE2 than other coronaviruses. So, N501Y and other mutations can ease the ability to spread. Around 70% more, still unproven, by increasing its epidemic power.

As we said four months ago (The many faces of a pandemic), we must not disregard the human factor’s participation. It is one of great importance in the British and world epidemiological disaster. The USA and Brazil are paradigmatic examples.

London and other areas in the U.K. have been in real epidemiological chaos. Due to many people’s irregular pandemic respect. It is not casual that the N501Y variant predominates in persons under 65 years old. A majority are young (Figure 2).

Figure 2. Covid-19 case reporting rate in England per 100,000 population and age group (16 December 2020). The age curves increase after September in people under 65 (and very young). Image credits: ECDC.

We must not disregard the human factor’s participation as one of great importance in the British. And also in the world epidemiological disaster.

For the moment, the coronavirus is only spreading more and better.

It is still unknown if the N501Y variant will have greater clinical aggressiveness. But it does not appear to affect current treatments or available mRNA vaccines. It is too early to conclude anything.

Time and chance will decide if the virus is learning to evade human defense mechanisms. In this scenario, it would need annual. Or a periodical vaccination like against seasonal flu. The effects of the vaccines’ pressure on the virus’s adaptive capacity are unknown. Another unresolved question is the role played by immunodeficient patients. They can take part in the genesis of mutations because of a prolonged time of infection. At least in some cases.

Mutations of SARS CoV-2 existed before. It exists now and will continue appearing in the future. Coronaviruses will mutate because of a genomic motto: mutate or die. The bad thing would be if viral mutations would lead to the death of many human beings.

It seems a good idea to get vaccinated when our times arrive.

Nurse vaccinating a person with one of the vaccines. Credit: The Associated Press.

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Agustín Muñoz-Sanz

Agustín Muñoz-Sanz

Medical Doctor (Infectious Diseases specialist/Professor of Medicine) and writer (narrative, theater).