Covid: mutations that make the delta variant of the virus more contagious and more worrying
The delta variant of the coronavirus was detected in India in October 2020 and has so far affected at least 96 countries. By July 4, 2021 the number had risen to 104. Kazakhstan, Laos, Latvia, Lebanon, Namibia, Oman and Sierra Leone are the latest countries to confirm the presence of the Delta variant.
In some of these countries it has become the dominant variant, as in the case of Singapore, the United Kingdom and Portugal.
Preliminary data shows that it is more transmissible than other variants, carries a higher risk of hospitalization and reinfection, and generates a slightly different symptom picture (more headaches and less coughing). , for example).
The delta variant is estimated to be 30 to 60% more transmissible than other variants of the coronavirus.
In the UK it has already become dominant and accounts for 90% of new cases.
This variant has raised concerns about the possibility of escaping vaccine protection, but this hypothesis has not been confirmed.
In other words, studies conducted so far show that vaccines remain effective against delta.
In Brazil, the city of São Paulo has already admitted that the delta is spreading into the city, but it is not known to what extent or if it will become dominant.
Covid: the Delta variant, what are the symptoms and the risks that it spreads so easily?
And according to some experts, it may soon become the dominant variant in the world.
So far, outbreaks have been confirmed in China, the United States, Africa, Scandinavia and countries on the Pacific coast.
Spread
The Delta variant, also known as B.1.6172, is known for its ability to replicate faster than others.
In the UK, epidemiologist Neil Ferguson of Imperial College London told reporters last week that the variant is almost 60% more transmissible than the alpha variant (B.1.1.7), which has been first detected in England.
Experts point out, however, that approved COVID-19 vaccines used in the United States, Europe and other countries appear to be effective in containing the spread of the Delta variant.
Is it possible that increasingly dangerous variants of Covid-19 will continue to emerge or is there a limit?
One of the main reasons this variant has spread rapidly around the world is its ability to bypass border controls and quarantine measures.
Even in Australia, which has stood out for its strict border controls, cases of the Delta variant have already been detected in Melbourne.
People can mistake the symptoms for a cold.
Another reason for the spread is the relaxation of restrictions and the fact that people are “tired” of social distancing.
Additionally, experts note, the Delta variant exhibits distinct symptoms that can easily be mistaken for a cold.
What are the symptoms
If the Indian variant appears to be more contagious than the other strains, it would cause symptoms typical of Covid-19. The director of the Institute of Genomics and Integrative Biology in Delhi indicates that the patients suffer from:
- headache,
- nasal congestion,
- runny nose,
- sore throat,
- muscle pain,
- diarrhea
“Stay home and get tested”.
“This variant seems to work slightly differently,” says the epidemiologist.
“People may think that they just had some sort of seasonal cold and that they continue to go to parties and that they can pass it on to other people.”
But what makes this delta variant more disturbing?
Generally speaking, this is a collection of genetic “enhancements” that facilitate the spread and invasion of the human body.
But we should not ignore the environmental issues at stake, that is, how the behavior of society without control and prevention measures also influences the transmission of these variants.
Mutations “advantageous” for the coronavirus
Sars-CoV-2, the coronavirus that causes covid-19 disease, is not as capable of mutating as the influenza virus, for example.
But when new variants appear, they must exhibit “advantageous” characteristics that make them viable in an environment where competition and selection are such that they can invade the human body.
In a presentation of the delta variant to the South African government, bioinformatician Tulio de Oliveira, director of the Krisp laboratory at the University of KwaZulu-Natal, South Africa, listed the main characteristics of the delta variant.
It is more transmissible and more likely to re-infect people who have previously been ill with other strains, but it is not yet clear whether the delta strain causes more serious illness or if it escapes the protection offered by vaccines.
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Oliveira also lists three groups of relevant delta variant mutations:
Two substitutions in the cell receptor binding domain (L452R and T478K).
substitution near the S1 / S2 cleavage site by furin (P681R)
substitution (T19R) and deletion (157-158del) in the NTD antigen domain.
But what does all this represent? Let’s see each of them.
1. More efficient cell invasion
A significant portion of these “beneficial” changes have occurred in the way the virus connects to our cells.
Specifically, the link between the viral spike (also known as protein S) and the ACE2 receptor, an enzyme found on the surface of our cells.
This spike acts as if it is the key that opens the lock on our cell and allows the coronavirus to invade it.
Once inside, it uses the cellular structure to multiply.
In the case of the delta variant, there are two relevant mutations in the cob, known as L452R and T478K.
But what do these numbers and letters mean? The first letter is the type of amino acid that existed before the change (L, symbol for lysine), the number is the location (452nd out of 1273 amino acids) and the last letter is the amino acid that came from in its place (R, symbol for arginine).
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During this virus production process, the surrounding amino acids can undergo three types of mutation: deletion (deletion), insertion (insertion) or change (substitution).
These mutations don’t happen for a specific reason and are often lost along the way.
But some of them become established and begin to appear as soon as the virus replicates.
This is the case for two key delta mutations: L452R and T478K.
The change from L to R at position 452 and the change from T to K at position 478 were found to be “beneficial” for the virus because they allowed the invader to better attach to the portal of entry (the enzyme ACE2).
This explains why this variant has become more transmissible.
Besides more efficient invasion, there is a tendency that the more viruses that invade cells, the more they replicate, which increases the viral load.
Therefore, more viruses will be transmitted through coughing or sneezing, for example.
A study by researchers from the Centers for Disease Control and Prevention of China found that a person infected with the delta variant can have up to 1,000 times more virus in their body than a person infected with the former. versions of the coronavirus at the start of the pandemic, at the end of 2019.
This higher viral load may also be associated with greater disease severity, as the variant tends to affect more human respiratory cells.
2. More efficient activation and theory of creation of coronavirus in the laboratory.
In order to invade the human cell, it is not enough for a virus to find a gateway and attach itself to it: it must first be activated.
In the case of Sars-CoV-2, this activation takes place via an enzyme in the human body (called furin) which cuts the tip of the coronavirus in two: S1 and S2.
After this cut, called cleavage, part of the ear (S1) attaches to the human cell and the other (S2) fuses its membrane with that of the human cell, allowing the insertion of genetic material and initiating the production of more viruses.
By cutting the cob, the enzyme causes it to open up and reveals hidden genetic sequences that help it bind more tightly to cells in the human airways, for example.
A mutation near this location can further alter this behavior.
This is the case with the delta variant, which carries a mutation (P681R) in this region.
“The more sensitive humans are to furin, the more efficient the virus peak will be. This furin-activated fusion process is mediated by the area from amino acid position 618 to amino acid position 1273” , explains virologist José Eduardo Levi, research and development coordinator of the Dasa laboratory network and researcher at the Institute of Tropical Medicine at the University of São Paulo (USP).
“A mutation in this region, such as P681R, makes this fusion faster. This mutation appears in the delta and alpha variants, discovered in the UK, and in some cases in the gamma variant, discovered in Brazil,” he adds. -he.
Mutations in this region of the coronavirus are so important that they are at the heart of two focal points of the pandemic.
First, this affinity for human furin would have been crucial in allowing the virus to escape from other animal species and start infecting humans in late 2019.
Second, this mechanism is so efficient and atypical among the types of coronavirus that infect humans that it has become the main argument for those who claim without evidence that Sars-CoV-2 was generated or modified in the laboratory.
“All coronaviruses that infect humans have a certain domain, a specific area that recognizes furin,” says Levi.
“But Sars-CoV-2 is very humanized. In other words, it is much more effective than what has been observed in other coronaviruses, which have reasonable recognition of furin.”
“And only Sars-CoV-2 has this mutation, this insertion of four amino acids. This is the strongest argument to say that this coronavirus was created in the laboratory.”
“Because so far no intermediate coronavirus has been found, which indicates that it has been improved gradually. It has arrived ready to be segmented by human furin,” adds the scientist.
According to the expert, the absence of this sequence of four amino acids in the Sars-CoV coronavirus may explain why it caused an outbreak of Sars limited to Asia in 2003, which did not turn into a pandemic that is spread worldwide as Sars-CoV-2.
http://cleverlysmart.com/covid-variants-sars-cov-2-variant-voc-alpha-beta-gamma-and-delta-and-voi-epsilon-zeta-eta-theta-iota-kappa-lambda/
3. Partially escape antibodies and vaccines
Fernando Spilki, professor at Feevale University and coordinator of the Corona-Ômica network at the Brazilian Ministry of Science, Technology and Innovation, uses the analogy of Lego parts to explain the role of mutations in the possible escape variants of the immune system and vaccines.
To learn how to defend themselves, defense cells, like neutralizing antibodies, use parts of the invaders to learn to identify and fight them.
When mutations occur in the coronavirus, for example, it is as if the parts of the antibodies no longer match those of the invader, allowing it to escape more easily.
Therefore, at the same time, the virus can mutate to attach itself more effectively to the entry gate of the cell and partially escape the engagement of neutralizing antibodies.
For Spilki, “it is as if the virus has created pathways to escape the immune system and developed more efficient means of transmission.”
He explains that all of these changes were “predicted” in laboratory experiments, which are able to analyze the influence of each exchange, insertion or deletion of these small pieces on the behavior of the coronavirus.
In the case of the delta variant, the mutations linked to it are the T19R substitution and the 157-158del deletion.
To return to the analogy of the Lego pieces, the substitution of the amino acid T (threonine) by R (arginine) in position 19 makes it difficult to identify the invader by the body’s defense system and its fight.
The same goes for the “missing” amino acids at positions 157 and 158.
Usually proteins have two ends, one called N-terminus and the other C-terminus.
In the case of coronaviruses, the N-terminal region (NTD) is considered to be more antigenic or immunogenic.
In other words, the human defense system “detects” it better and produces more antibodies against it.
The tip (S protein) is the most antigenic of these, so vaccines are usually produced targeting this structure to teach the body’s defense system to identify it in order to fight the coronavirus as a whole.
This is where the mutation comes in as a way to hamper the fight against the coronavirus.
The modifications (deletions and substitutions) of the structure of the delta variant in an antigenic zone (DTN) make it difficult for the body’s defense system to act.
“Why the hell would she start removing parts of her genome? There must have been a powerful reason for that. What? The human immune response, whether natural from infection or induced by a vaccine,” says Levi. .
“In general, the deletion is detrimental, that is, it renders the virus ineffective and ends up killing it. But in the case of the coronavirus variants, these deletions are advantageous because they eliminate regions that cause a very strong immune response in the host and thus manage to escape (the human defense system), “he adds.
So far, it has been proven that the delta variant can escape the antibodies of people who have already been infected with the beta variant (discovered in South Africa).
But nothing yet proves that it is able to escape the immune response generated by vaccines.
It should be remembered that none of these mutations is specific to one or the other of the variants. What makes them worrying is their combination.
That is to say, they have at the same time new characteristics that make them better at invading cells, more effective at activating and escaping the defense system.
According to Levi, the background of multiple variants having random mutations that are relatively similar is called evolutionary convergence.
Indeed, among other reasons, the evolutionary pressure of natural selection against the most diverse forms of coronavirus around the world is virtually the same: people gain immunity, either through the vaccine or because they have been infected with it. the virus.
Source: PinterPandai, Aljazeera, NYmag, BBC, The Conversation, Web MD, Imperial College London
Photo credit: Kicknews
