Are the strains more dangerous to wait for the Delta? There are clues in viral evolution

Last October, somewhere in India, a manprobably immunocompromised, possibly taking medications for rheumatoid arthritis or advanced HIV / AIDS, have contracted COVID-19. His case may well have been mild, but due to the inability of his body to rid itself of the coronavirus, he lingered and multiplied. As the virus replicated and moved from one cell to another, pieces of genetic material copied themselves incorrectly. With this modified virus, he infect others. This is how, according to scientists, the Delta strain of coronavirus arose, which is wreaking havoc around the world and claiming a huge number of lives every day. During the COVID-19 pandemic, thousands of variants of this virus have already been identified, four of which are considered "of concern" - Alpha, Beta, Gamma and Delta. The most dangerous of them is Delta, according to some reports it is about 97% more infectious than the original coronavirus, which appeared in 2019 in Wuhan. But, can there be even more dangerous strains than Delta? Understanding how mutations arise will help answer the question.

Coronavirus mutations stink during replication as it spreads in cells

Coronaviruses are more susceptible to mutations than other viruses

Such a turn of events as in India formicrobiologists was not a surprise. Of course, they could not predict where and when an even more deadly virus would appear, and whether it would happen at all, but the possibility of a dangerous mutation was fully admitted. According to Bethany Moore, chair of the Department of Microbiology and Immunology at the University of Michigan, every time a virus enters a cell, it replicates its genome to spread to other cells.

Moreover, coronaviruses copy their genomes morecarelessly than humans, animals, or even some other pathogens. That is, in the process of copying their own genetic codes, they often make mistakes, which leads to mutations. Although, there are viruses that mutate even more often than the coronavirus, for example the flu. This is because the RNA of coronaviruses contains a proofreading enzyme that is responsible for double-checking copies. Therefore, most often in what form it gets into a person, in this way it comes from him.

Coronaviruses copy RNA carelessly, resulting in mutations

However, as epidemiologists say, to inflictirreparable damage to the world, many incorrectly copied copies are unnecessary. Viruses that are transmitted by airborne droplets, for example, during a conversation, spread much faster than those that are transmitted sexually, through blood, or even tactilely. In addition, such viruses have another danger - an infected person can transmit it, and even its mutated version, even before he knows about his infection.

Individual mutations of the coronavirus are less dangerous than convergent evolution

Most mutations either kill the virus on their ownthemselves, or they die due to lack of spread, that is, the carrier passes it on to a small number of people who isolate themselves and prevent the virus from spreading further. But when a large number of mutations are created, some of them accidentally manage to "break out" from a limited circle of carriers, for example, if an infected person visits a crowded place or an event with a large number of participants.

However, according to Vaughn Cooper, professormicrobiology and molecular genetics, scientists are most afraid of not even a mutation of any one virus, but similar changes that occur in many independent variants. Such changes always make the virus more perfect in terms of evolution. This phenomenon is called convergent evolution.

For example, in all the strains mentioned abovethe mutation has occurred in one part of the spike protein (spike protein). These protrusions help the virus infect human cells. So, as a result of the D614G mutation, one type of amino acid (called aspartic acid) was replaced with glycine, which made the virus more infectious.

Most coronavirus mutations occur in the spike protein

Another common mutation known asL452R, converts the amino acid leucine to arginine, again in the spike protein. Given that the L452 mutation has been observed in more than a dozen individual clones, it can be concluded that it provides an important advantage to the coronavirus. This assumption was recently confirmed by researchers after sequencing hundreds of samples of the virus. Moreover, as scientists suggest, L452R helps the virus infect people with some immunity from the coronavirus.

Since the spike protein was criticalfor the development of vaccines and treatments, scientists have carried out the largest number of studies to study mutations in it. But some scientists believe that the study of mutations in the spike protein alone is not enough to understand the virus. In particular, this opinion is shared by Nash Rochman, an expert on evolutionary virology.

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Rohman is a co-author of a recent article inwhich says that, although the spike protein is an important element of the virus, there is also another, no less important part of it, which is called the nucleocapsid protein. It is a coating that surrounds the RNA genome of the virus. According to the scientist, these two areas can work together. That is, a variant with a mutation in the spike protein without any changes in the nucleocapsid protein may behave quite differently from another variant that has mutations in both proteins.

A group of mutations working in concertcalled epistasis. Simulations by Rohman and colleagues show that a small group of mutations at different points can help the virus escape antibodies and thus make vaccines less effective.

The threat of a dangerous mutation of the coronavirus will remain until the end of the pandemic

The greatest concern of scientists is thatthe fact that mutations occur that are resistant to vaccination. All vaccines are currently showing their effectiveness. However, the latest Mu variant has already proven to be much more resistant to them than all previous strains, including the Delta variant.

Considering that a smallpart of the world's population, the virus has no particular need for a mutation that can completely outsmart the immune system. Experts believe it is easier for the virus to find new and better ways to infect billions of people who do not yet have immunity.

Vaccination is one way to stop a pandemic and thereby reduce the likelihood of a dangerous mutation

However, no one knows what mutations await.ahead and how much damage they can cause. Given the long incubation period, a virus with a dangerous mutation can survive and disperse around the planet, even if it originates in a sparsely populated area.

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Understanding the issue of mutations, it is important to understand one thing- they occur when there is viral replication. Mutations emerging this year in different countries are the reason the pandemic is not yet under control. That is, the more the pandemic rages, the more mutations arise, which in turn contribute to the further spread of the virus. Therefore, the best way to prevent the emergence of future, more dangerous strains is to limit the number of replications. At the moment, vaccination helps in this, as well as compliance with preventive measures.