Time 24 News (EUA)

Sequencing coronavirus was only possible with public investment, says scientist

Publicado em 05 março 2020


On February 26, Brazil registered the first case of coronavirus, becoming the first country in Latin America to register a case of the epidemic.

Last Tuesday, the undersecretary of Health Surveillance, Wanderson de Oliveira, announced that so far 488 suspected cases of the disease have been registered. So far, Brazil has confirmed three cases of the epidemic, all in São Paulo.

The report of the World Health Organization (WHO), last Monday points out that Covid-19 is present in 64 countries and the fatality rate is 3.4%.

Researchers from the Adolfo Lutz Institute (IAL) and the Institute of Tropical Medicine at the University of São Paulo (IMT-USP), public institutions based in São Paulo, carried out the virus sequencing process, 48 hours after the confirmation of the first case.

“As soon as the first positive case appeared, we were all prepared, the whole team was ready. Then, the sequencing was done in real time. We have already been analyzing it, sending the data to the University of Oxford, University of Edinburgh and Birmingham and the whole group was able to do this as quickly as possible so that we could release this result in 48 hours ”, reports biomedical Ingra Morales Claro, 28 years old.

Biomedical and doctoral student at the Faculty of Medicine of the University of São Paulo (USP), she was part of the team led by Professor Ester Sabino and composed of nine women and one man.

“We go through difficulties in this macho world, but we are women, smart, scientists. So, it is a very wonderful group made up of wonderful women, led by Professor Ester, who is our inspiration within the laboratory ”, she points out.

The researcher highlights the importance of encouraging the São Paulo State Research Support Foundation (Fapesp) to work on genome sequencing and reinforces the need for government investment for this work.

“We are encouraged by a project called Cade [Centro de Diagnóstico Distribuição Genômica e Epidemiologia de Arbovírus], from Fapesp. Only with this money is it possible for us to work with this technology all the time. We have always had an incentive from Fapesp and all students who participated in the genomic sequencing have scholarships. So government incentive and investment in research is the most important part at the moment ”, he points out.

In an interview with Brasil de Fato, she spoke of the role of genomic sequencing and its importance in epidemic cases as well as the recognition of the role of women scientists.

Brasil de Fato: Your group is practically made up of women. How is this being perceived by the team?

Ingra Morales Claro: The group of professor Ester Sabino, who is our advisor and coordinator of this CADE project in Brazil, is composed of nine women and one man. We are very happy for this recognition of the female scientist. We are receiving a lot of messages from people who are asking what it is like to be a woman in this direction of science and a lot of girls, who are joining now and in science are mirroring us. So, it’s been very nice to see this and to be able to pass it on to women in Brazil, that we are going through difficulties in this macho world, but we are women, smart, scientists. So, it is a very wonderful group composed of wonderful women, led by Professor Ester, who inspired us within the laboratory.

How was the specific work process for coronavirus sequencing?

We managed to be prepared for this Corona epidemic. We were already together with the Instituto Adolfo Lutz analyzing the suspected cases and as soon as the first positive case appeared, we were already prepared, the whole team was prepared. Then, the sequencing was done in real time. We have already been analyzing it, sending the data to the University of Oxford, University of Edinburgh and Birmingham and the entire group managed to do this as quickly as possible so that we could get this result out in 48 hours.

When Brazil started to perform genomic sequencing?

Since 2016 when there was an epidemic of the Zika virus in Brazil, we received a researcher from the University of Birmingham at our institute and he brought this technology, called MinION, which is a portable sequencer. I learned this technology in 2016. I participated in a project called Zibra, in which we traveled around the Northeast, inside a minibus and sequenced the Zika genome inside that bus. Since then, our institute has been using this technology.

Which sequencing was used for which diseases in the country?

Epidemics of dengue, yellow fever, chikungunya and zika. We have been using and improving the sequencing protocol, I myself spent a few months at the University of Birmingham working on it so that the technology would be faster and cheaper and brought it here to the Institute.

How important is genomic sequencing?

Sequencing gives us important information about the virus. We can see the mutations that happen in this genome from person to person. From there, we can analyze the dispersion of the virus because, depending on the time and place, we can analyze these mutations and use this genome later to make vaccines, produce drugs and produce diagnostic tests. So, we have a lot of information that is generated from genomic sequencing.

How does sequencing help to contain an epidemic such as the coronavirus?

We are using it a lot today to see this distribution of the epidemic. Only with genomic sequencing could we know that our sequence was similar to that of Germany and the second with that of England. Only this technology allows us to observe this.

What types of support are needed for Brazilian science to allow sequencing?

Genomic sequencing is a technology that is still expensive at the moment. This is what we have been working on. Over the years, it has been reducing the price a lot, but it is still an expensive technology to be used in Brazilian diagnostic research centers.

This is our idea, to make it less complex, cheaper, to distribute this technology to all centers in Brazil, so that everyone can use it, but even so it is still expensive compared to other diagnostic tests.

Do you receive any support from the government?

We are encouraged by a project called Cade [Centro de Diagnóstico Distribuição Genômica e Epidemiologia de Arbovírus], from Fapesp. Only with this money, we can work with this technology all the time. We have always had an incentive from Fapesp and all students who participated in the genomic sequencing have scholarships. So government incentive and investment in research is the most important part right now.

For vaccine and medication production is sequencing always used or is it just one of the ways?

I am not very specialized in this area of ??vaccines and medicines, but they do use genomic sequencing. Because if the virus mutates somewhere, some drugs sometimes stop working. In that case you have to make a new medication. This genomic sequence is needed to analyze these genomes and see these mutations, to see if the drug and vaccine are still effective for that virus.

It is believed that the greatest compatibility of the coronavirus genetic material was with a virus sequenced in Bavaria, Germany. Does this mean that the contamination was in Germany? Or is it just an indication?

This is just an indication, it shows us that it is similar, the sequence generated from Bavaria, from Germany, but it does not mean that it came from Germany, because the sequences are generated and the mutations happen over time. So, for us to indicate that it came from Germany, from Bavaria, from some patient, for example, infected, we would need, in this case, to have sequenced all the positive cases, so we would be able to track this dissemination, but as we do not have these data, we cannot sign this.

What are the other ways to identify the source of the virus?

We can affirm based on the patient’s history, for example. This patient had contact with a patient from Germany and was contaminated by that patient, which was the case with our sequences. We knew that the patient came from Italy. Or else, we would have to have all positive cases sequenced, so we would be able to fully know the dissemination of these cases.

Is this mutation issue one of the characteristics of the virus that causes it to become an epidemic?

Mutations always occur in a virus, especially RNA viruses, which is the case. When a person is infected, this virus begins to replicate within our body and will always mutate as it replicates.

Each virus has a different mutational rate, but this is very common, which is why we are able to do all of these analyzes and why these new viruses are always appearing, because of mutations that sometimes only infected animals and then case it mutated and started being transmitted to human.

Are the viruses that attack the respiratory system the most mutated?

To respond more appropriately, I would need to analyze the mutational rate of each virus. But influenza is more mutable than coronavirus, for example, and other types of viruses like arbovirus, which are viruses transmitted by the bite of a mosquito that also undergoes many mutations. To analyze this with certainty, it is necessary to analyze viruses for viruses and analyze their mutational rate.

The sequence obtained by you has what percentage of coverage? Does this already constitute a complete genome of the coronavirus that is in Brazil?

In the first genome we got 96% coverage and the second genome 100% coverage. This gives us what we call the complete virus genome. In the first case, we had a slightly lower percentage, because the viral load that the patient had was slightly lower than that of the second patient and this makes it difficult to amplify the genome in the tests that we do.

The sequencing was done with the remote collaboration of researchers from the universities of Birmingham, Edinburgh and Oxford, in the United Kingdom. How is this remote work?

We have this group, Cade, in which we have been working together for some years: USP, University of Birmingham and University of Oxford. At the time of the sequencing, we were with them via computer. Everything that was being generated, we passed it on to them. So it was a group that actually managed to make that result fast.

How does your partnership contribute to society and people’s health?

This is a very important partnership for us. It has always been, since 2016. If it weren’t for this partnership, we wouldn’t have learned the technology, wouldn’t have passed this technology on to other institutes, wouldn’t have worked together, improved the analyzes, the protocols, wouldn’t have all this investment that we has been doing in the research that we have been doing.

We have this partnership, so we have great researchers and very important researchers from Oxford, like Nuno Faria from Birmingham, among others. They pass this knowledge on to us, we have been working with workshops to teach this everything we have been learning. So, it is very important because we are doing technology cooperation and we are trying to pass it all on to the research and diagnostic institutes here in Brazil.

Can we say that this sequencing is a way to contain the epidemic?

It would not contain the epidemic, but it would help to study the epidemic better. In the case of Yellow Fever, for example, we were analyzing the cases and managed to do mathematical studies to see how long this epidemic would arrive elsewhere. See this spread through the cities to see the question of vaccination, which city was at greatest risk, which needed vaccination as soon as possible. In cases of an epidemic, genomic sequencing is important because of this.

What types of viruses exist?

We have RNA and DNA viruses. RNA is when it is a single strand, DNA is when it is a double strand. So, we only have a virus strip containing genetic material and that is why they need a host for them to replicate.

Are both viruses parasites?

The two viruses, both DNA and RNA, are mandatory parasites, so they need our machinery in order to replicate. In this case, RNA has a single strand, so it replicates within our body, using our machinery and is more likely to undergo mutations, when compared to DNA.

Examples of RNA viruses are influenza, corona, some arboviruses such as zika, dengue and chicungunha and of DNA we have, for example, herpes.

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