Long before the first official case of coronavirus appeared in Brazil, scientists in the country were already looking for a cure or treatment. Since the end of January, Brazilian researchers from Cnpem (National Center for Research in Energy and Materials), in Campinas (SP), have been investigating drugs that can help those who fell ill in Covid-19. Less than two months after the start of the tests, which involved more than 2,000 candidates for treatment, five options remained the most promising. A new phase of testing now begins.
Cnpem, where most of the research is done, is an independent research center, but supervised by the MCTIC (Ministry of Science, Technology, Innovations and Communications). It has national laboratories for nanotechnology, biosciences, biorenovables and synchronous light, the latter being responsible for one of the most advanced particle accelerators in the world.
The search for a drug involves the “repositioning of drugs”. What is it? They select drugs that are already on pharmacy shelves, therefore already approved for human use. From the initial 2,000 – were analgesics, antihypertensives, antibiotics and diuretics, among others – the number dropped to 16 and, subsequently, to five more promising, cheap and available drugs in the Brazilian market.
The researchers’ intention was to see if any of the thousands of selected drugs could interact with the protease [um tipo de enzima] of the coronavirus to prevent its replication in the human body. At this stage of the research, analyzes and computer simulations with artificial intelligence were made to understand which drugs could inhibit the enzyme and function as an antiviral.
“This fit doesn’t happen easily. It’s like looking for a key [medicamento] on a keychain full of them [muitos compostos]. This key must fit the virus lock perfectly [locais específicos das proteínas dos vírus capazes de bloquear sua atividade]”, tells the Tilt Daniela Trivella, scientific coordinator of LNBio (National Biosciences Laboratory) at Cnpem.
“These specific regions of viral proteins are important for carrying out chemical reactions, infecting human cells and propagating viral genetic material – fundamental stages of an infection. That is why it is these locks that we aim for”, points out Trivella.
With the five compounds selected, the research enters a new phase of analysis in vitro – in cell culture with direct contact with the virus. The intention is to see, in practice, how the selected compounds and drugs interact with the coronavirus. The name of the compounds at this stage will not be informed to avoid running to pharmacies, as the study is not yet complete.
There is still no forecast of completion of the tests, since they are in the initial phase. But Cnpem researcher Rafael Elias Marques highlights that we already have a lot to celebrate in the fight against the coronavirus.
“The fact that we found a drug like chloroquine and hydroxychloroquine which, when combined with azithromycin, apparently has a protective effect, is great news. It means that, even though the coronavirus is a highly infectious organism, the treatment is possible. A first victory like this is motivating “, he says.
In the Brazilian study, chloroquine will be placed as a “positive control” in the experiments after two international studies indicate that it is able to reduce the replication of coronavirus in vitro.
Still, Marques criticizes the consumer search for chloroquine in pharmacies after it was cited by US President Donald Trump, which caused a shortage for those who really need the drug to treat other diseases.
“There was not the slightest need for people to go shopping, emptying pharmacies of this medicine. Nor for people to declare that a cure had been found. There is still a very long way to go,” he explains.
But as there is a huge national and international movement, it is likely that we will find something that at least reduces the suffering that the virus causes.
Rafael Elias Marques, CNPEM researcher
The Brazilian study started with four people, went to six and now there are 11 in the project. In times of isolation, only researchers linked to the coronavirus are following the work directly at Cnpem, while others stay at home offices. In fact, social detachment is one of the challenges in finding the right medication.
“Isolation is a problem, but it is necessary to stop spreading. Universities and Cnpem are working with minimal staff. This makes it somewhat difficult, research starts to run at a slower pace, because we are a smaller number of people working The biggest problem is that eventually we will have a limitation in inputs for research, precisely because of the difficulty and demand worldwide for reagents that we will also use “, he says.
Studying a virus, especially something new like Sars-Cov-2, is not just one step. According to Murilo de Carvalho, a Cnpem researcher, organisms of this type need to be studied from several points called in the scientific community “omics” —or “omics” in Portuguese.
“The first thing is to always try to understand the logic behind biology. […] So I go through the genomics part [código genético do vírus]proteomics [proteínas]metabolomics [como proteínas agem]… “, he explains.
In the research, Rafael Elias Marques evaluates having the help of electronic cryomicroscopy, a recent chemical technique that won the Nobel Prize in 2017. Cnpem has such equipment at LNNano (National Nanotechnology Laboratory). This huge microscope is valued at millions of dollars outside Brazil.
The electronic cryomicroscopy technique allows investigating organisms and substances from their interaction with electrons. Cnpem’s most advanced equipment allows structures to be placed at a temperature of nitrogen to record images and understand what happens inside organisms and what interactions can happen.
“Today, large groups of structural biology have used this equipment. They take the coronavirus. In less than a month, one of the groups that was working in the area managed to produce structures linked to the coronavirus. This might not even have been feasible in the past”, says Rodrigo Portugal , researcher at Cnpem.
The Cnpem survey is just one among several that take place in Brazil. In drug tests, hospitals in São Paulo said they would start research with hydroxychloroquine – in this case, these are clinical tests and different from those performed in Campinas.
Outside of Brazil, WHO (World Health Organization) also organizes a race to find a cure for the disease, with the participation of at least ten countries. This study will also be clinical, with direct testing on patients.
Other fronts also try to attack the coronavirus in Brazil. There are researchers working on formulating better diagnoses for the disease, as well as others looking for vaccines against Covid-19.
At this time, scientists have come together and have relied on exchanges of information. Rafael Elias Marques highlights some key moments, such as the first isolation of the virus in Brazil, made by USP professor Edson Durigon and shared with other researchers. Currently, Cnpem researchers use Unicamp facilities for in vitro tests, as they have the necessary level of biosafety.
MCTIC also recently created the Virus Network, which includes several universities and institutions that investigate the disease, with exchanges of information between the teams.