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Virologist Marta Giovanetti has closely followed two of the three variants of the coronavirus that have been worrying the world in recent weeks.
The Italian scientist arrived in Brazil in 2015 and has already carried out research on the genomes of chikungunya, Zika, dengue, yellow fever and, since last year, Sars-CoV-2.
She is the resident researcher in the country with the highest number of publications on covid-19 and the most cited, according to a survey carried out in October by the USP’s Academic Information Management Agency. At that time, it had 26 published studies and 633 citations.
In addition to working in the Flavivirus Laboratory of the Oswaldo Cruz Institute (IOC / Fiocruz), in Rio de Janeiro, he also collaborates with a laboratory in Italy and with the Brazilian who is in charge of the coronavirus genomic surveillance program in South Africa, Tulio de Oliveira, director of the Krisp laboratory at the Nelson Mandela School of Medicine.
Both Brazil and South Africa have recently identified new strains of the coronavirus that may be more transmissible and even elude the antibodies of those who have already had the disease the first time, causing reinfections. Along with another strain identified in the UK, they are of concern to health officials around the world.
In an interview with BBC News Brazil, the researcher explains the risks posed by these variants, tells a little about their trajectory and draws attention to the study that detailed the first case of reinfection by a coronavirus line that can “circumvent” the immune system . , in which the patient had more severe symptoms of covid-19.
The N501Y and E484K mutations
Today, at least three variants of Sars-CoV-2 cause concern, according to the WHO: B.1.1.7, identified in December in the UK, 501Y.V2, found in South Africa, and P.1, which emerged in the Amazon. .
Scientists’ attention is focused on two mutations in particular: N501Y, present in all three variants, and E484K, found in South Africa and circulating in Brazil.
Both are located in genes that code for the beak, the protein responsible for interacting with the host cell and that, in practice, facilitates the entry of the coronavirus into human cells.
In the case of N501Y, there are signs that it may make Sars-CoV-2 more transmissible: more contagious, the virus could land more people in the hospital and increase the number of deaths. However, there is no indication that the mutation results in a more severe version of Covid-19.
In the case of E484K, shared by the Manaus and South African variants – and another one identified in December in Rio de Janeiro, called P.2 – studies have shown that it can hinder the action of antibodies.
It modifies a region of the spike known as RBD (receptor-binding domain), which binds to the receptor on human cells, and exactly where neutralizing antibodies produced by the immune system act.
With the change, the antibodies lose their specificity with RBD and the virus has an escape mechanism from our immune system, which becomes more difficult to act.
These findings have raised concerns about a possible effect on vaccines. For now, it is believed that they do not lose their effectiveness, but they may have reduced effectiveness.
“But many more studies will be needed to really understand whether or not these variants can have a major impact on vaccines. We cannot ‘do terrorism’ at this time,” added Giovanetti.
In any case, the alert issued by these discoveries is already very clear: on the one hand, it is necessary to maintain measures to control the pandemic, such as social detachment, and accelerate the vaccination process to reduce the possibility of its circulation and possible future strains. says the scientist.
The greater the freedom of movement of the virus, the greater the probability that it will mutate.
Dodging the immune system
The E484K also caught the scientist’s attention in a study she recently participated in, which identified the first case of covid-19 reinfection by a variant with this mutation.
“Our study opened several other questions, because the second case was a little more severe than the first,” he says, noting that most of the Sars-CoV-2 reinfection cases described so far showed a second milder episode. First.
She was a 45-year-old health professional with no comorbidities residing in Salvador, who had the disease in May and then in October, each episode caused by a different variant of the coronavirus.
In the first, he had diarrhea, headache, weakness, and pain when swallowing for about 7 days.
Months later, infected by the coronavirus strain identified in December in Rio de Janeiro, now called P.2, the symptoms evolved into a cough, sore throat, loss of taste, insomnia and shortness of breath. However, she did not need to be hospitalized and she recovered.
The work, led by researcher Bruno Solano, from the Instituto D’Or de Ensino e Pesquisa and the São Rafael Hospital, was published in January in a non-peer-reviewed version and sent to the scientific journal Lancet.
“The study raises questions about the issue of reinfection and the clinical severity associated with this mutation. It is an open question and more research is needed.”
The P.2 variant has a single peak mutation, E484K, while the P.1 – initially found in Amazonas but already detected in other states, such as São Paulo – has a higher number of mutations in the protein that binds to the human cells and thus has generated even more concern.
Hundreds of different strains
Marta also explains that, despite concern about new variants, mutations are abundant in viruses.
These changes in the genetic code of pathogens appear when they multiply, they copy themselves. They are “errors” in the transcription of the genetic code, in the case of Sars-CoV-2, of RNA.
And they may end up being important to the virus precisely because they can make it resistant to the host’s immune response.
“We have to think that they are obligatory intracellular parasites: they cannot survive outside a cell, outside a host. If they don’t change, the host becomes resistant and cannot survive. Therefore, these mutations are necessary for it to survive. guarantee their own survival, ”he illustrates.
Most mutations, however, are irrelevant, some are even detrimental to the survival of the virus.
To give you an idea, even though the planet is discussing four or five variants of the most worrisome coronavirus, there are almost 1,000 registered by scientists from around the world on the Pangolin platform, an acronym for “Phylogenetic mapping of named global shoot lineages“and also the name of one of the animals that, as investigated by science, may have served as an intermediate host for the new coronavirus.
Six years of outbreaks and epidemics in Brazil
With a degree in biology, with a master’s degree and a doctorate in the area, Marta says that she has always been interested in viruses.
“It was incredible to me to think that these little particles were able to replicate as if they had been programmed by some mysterious algorithm.”
And it was also in Rome where he had contact with researchers Luiz Alcântara, then from Fiocruz in Bahia, and Tulio de Oliveira, who has been working in South Africa since 1997, in an international cooperation project to carry out the molecular characterization of HIV and HTLV. both in Brazil and South Africa.
Then came the opportunity to come to Brazil, in 2015. Since then, the work of the researcher, who lives in Rio de Janeiro, has adapted to each new outbreak or epidemic that occurs here.
He was studying the spread of the chikungunya virus when the Zika epidemic broke out.
At that time of crisis, Alcântara, now in charge of the Oswaldo Cruz Foundation’s Flavivirus Laboratory, joined national partners, such as immunologist Ester Sabino, and international partners, such as Oliveira, in South Africa, and the British universities of Oxford and Birmingham, in the Zibra project, which aimed to carry out real-time molecular characterization of the virus that had been causing microcephaly in newborns.
With the team, Marta traveled northeast in a mobile laboratory to study the pathogen’s genome.
The technology used in this project, a portable genome sequencer called MinION, would be critical years later in the COVID-19 pandemic. It was with him that Sabino’s team, a researcher at the Institute of Tropical Medicine of the USP School of Medicine, would sequence the first Sars-CoV-2 genome in Brazil at the end of February.
“The implementation of this technology was fundamental, because it became a technique to allow active real-time monitoring of viral pathogens,” says Marta.
After Zika, remember, there was a resurgence of yellow fever in the southeast and, in parallel, large outbreaks of dengue.
In 2020, he adds, the coronavirus arrived and everything changed in scale. Researchers have been working almost continuously for more than a year and the production and exchange of knowledge has no parameters.
In 12 months, he points out, more than 400,000 complete Sars-CoV-2 genomes were generated, “perhaps a tenth of the number of complete genomes we have for the dengue virus, which has been endemic for decades in Brazil.” – a fundamental work for the development of vaccines in record time.
