Covid-19 is a disease that makes no distinctions between people, has infected millions, and killed hundreds of thousands, on all continents. Each country presented a different response to the threat, according to its capacities, and the practice of social isolation, under the guidance of the World Health Organization (WHO), a measure adopted by practically all countries where the virus arrived, however, the efficiency of isolation depends on two factors: the timing of the decree for the closure of services and guidance on isolation, that is, the right time to isolate - preferably before the virus spreads without control - as well as the population's own social responsibility for the threat and their willingness to obey the guidelines of health authorities.
However, social isolation is a preventive measure, which seeks to function as harm reduction, since it is impossible to prevent contamination, but with the objective that these contaminations do not reach a large number of people, and overburden hospitals. Brazil, for example, is experiencing a constant political crisis between the three powers and friction between the position of the federal executive and the states, in addition to the fact that in the vast majority of states people have not satisfactorily fulfilled social isolation, which has meant that isolation alone was not enough to stop transmissions and, consequently, deaths. Brazil until the beginning of July was still the second country with the highest number of cases and one of the most registered new cases in the world.
While the coronavirus pandemic continues to make victims and infect new people around the world, efforts to find faster and more effective means of prevention and treatments are emerging in several countries. Scientists are looking for answers to diagnoses, preventive, therapeutic, and vaccine interventions. With the demand for answers from the scientific community that the disease has been causing, the lines of research are mostly focused on treating the disease and developing vaccines. Never has the world watched in real time the joint work of so many actors to defeat a pandemic, and the biggest challenge is the search for quick answers, at a pace opposite to the traditional and careful research dynamics.
In this race against time, studies have appeared with several drugs, such as chloroquine and hydroxychloroquine. These substances quickly gained fame, since they had space in the media debate through the attention given by the President of the Republic and his supporters. Laboratory experiments carried out on cells have attested that these compounds used against malaria and autoimmune diseases have an immunomodulatory effect - they provide an increased immune response against certain microorganisms, so it is used to treat autoimmune diseases such as lupus and rheumatoid arthritis. However, weeks later, studies conducted in China and Europe raised doubts about the effectiveness of chloroquine - and even pointed out serious side effects, such as arrhythmias. In addition, while some tests indicated improvement in patients, others point out that the drug made no difference in treatment.
Other potentially promising substances are advanced in research, such as azithromycin, an antibiotic with antibacterial effect, commonly used to fight diseases of the respiratory tract; in the case of covid-19 being used in conjunction with chloroquine and hydroxychloroquine and remdesivir, approved in the United States for use in treating patients with covid-19 in serious condition. Both have not yet been definitively passed safety and efficacy tests for use.
Among so many different lines of research, exciting news has emerged in Piauí. Researchers from the Computational Quantum Chemistry and Drug Planning Group at the State University of Piauí (UESPI) identified substances found in the oil extracted from the fruit of the buriti with the capacity to possibly inhibit the enzymatic system of the coronavirus. The project is under the guidance of Professor Dr. Francisco das Chagas Alves Lima, a researcher who works as a professor of Chemistry at the State University of Piauí (UESPI) and guides the Graduate Program in Chemistry at the Federal University of Piauí (UFPI). The article with the results was executed by Professor Allan Costa, from the Federal Institute of Pará (IFPA), as part of his doctoral research, in partnership with researchers Ézio Sá (IFPI), Roosevelt Bezerra (IFPI) and Janilson Souza (IFMA) ), from the same group.
Today in the large pharmaceutical industries, the beginning of the research, when there is not much information on the object, for example on the culture of using a regional plant, is done a procedure called drug planning, as reported by Professor Francisco das Chagas Lima. Drug planning is done by bringing together a large group of molecules of the object, where an in-silico study is performed in order to see which of these molecules has the best interaction for the desired effects. Subsequently, an in vitro study is performed, where a cell is contaminated with another study object, in this case, the virus, and then which molecules have the best action to inhibit it are tested. The next step is called an in vivo study, where instead of the cell it is tested on an animal, with the same method of testing the molecules that react with the cell and with the verification of side effects, a step that is not yet clear in the previous phases.
“The great thing about the in-silico study, which appears in this first article that we publish, is that the need to use guinea pigs was reduced by 40% because now we have discovered 3 molecules with potential among the 9 presents in the oil, being unnecessary now continue testing with the others 6. These three molecules of buriti oil showed very good theoretical results of inhibiting the 2GTB peptidase structure, which is 96% similar to the main 6lu7 protease of covid-19, this 6lu7 protease is related to the cycle of the virus. Thus, the results with the 2GTB peptidase open the door to further studies of possible 6lu7 protease inhibitors using buriti oil. Unfortunately, for the advancement of research, Piauí has very few levels (2 and 3) laboratories to work with viruses. In Brazil, level 4 laboratories are only those of Instituto Butantan and Fiocruz, so there are not many laboratories that do research with viruses. In Piauí there is none where there may be an in vitro pre-study of viruses. A researcher friend from São Paulo contacted me about this issue, where he will be able to verify the in vitro study of these molecules”, reveals the professor.
Professor Francisco Lima explained to Sapiência that the in-silico study consisted of a computational study of the 3D molecules that are present in buriti oil and already known enzymes from Sars-CoV-2. These enzymes are available in the online database Protein Data Bank (PDB), from where the structures were downloaded.
“Within the enzyme there is a region called the active site, where biological interactions occur between the enzyme and the molecules, in this active site there are several chemical reactions, for example when a person takes an aspirin, there is a certain region in the enzyme where there is a chemical reaction between molecules, they leave the enzyme and are then eliminated by the excretory system, for example, urine or sweat ”, explains the researcher.
From there, two methodologies in the research started, first the molecular docking: a computational method that can find more likely ways of binding between a binding substance and a biological macromolecular receptor. The molecules present in the buriti oil were inserted in the active site and the docking was done through the computer program used, which showed the region where they interact and which amino acids are inserted in the process.
Then the study is done in molecular dynamics, no longer static, where the molecules are observed entering the active site of the enzyme, interacting the most important amino acids and leaving, with this it is possible to verify which amino acids better interact within the active site and which ones have greater potential for drug synthesis, for further study in vitro.
“Then the question arises: why the buriti oil? Basically, because we are already aware of several important actions of the oil: in addition to being a very rich food, it is repellent, a good healing agent, as well as pequi, it has an anti-inflammatory effect since both have fatty acids. In some cases, it is also used as a snake poison inhibitor. That is why we chose this substance, which is abundant in the northeast and north, also contemplating the Ph.D. student and IFPA professor, Allan Costa. In the North, these uses of buriti as traditional medicine are very common, hence the idea”, says the professor.
The professor explains that to inhibit the action of an enzyme or virus, it is necessary to find a molecule that prevents them from interacting or replicating with the biological environment. For the virus to develop it needs to be free of any molecules that hinder its activity, so if one finds a molecule or molecules that remain within the active site of the enzyme, it shows that this molecule has the potential to inhibit the action of the virus. At best, it prevents the virus from multiplying, as in the case of vaccines, or prevents it from interacting in the biological environment.
“The article we published will bring the details of this process, but to put it briefly: we found a molecule capable of preventing the virus from interacting in the biological environment, that is, with the receptor cells in which it would use to replicate, as it does not interact and is short-lived, it has no ability to reproduce and consequently dies without attacking cells as it normally does ”, details the researcher.
Currently, computational calculations are being prepared with the main protease 6lu7 of COVID-19, as explained by IFPA professor Allan Costa. “We are going to study how this protein behaves in relation to the molecules already studied with the 2GTB peptidase. We don't know if we will have good results, but we are confident. And who knows, maybe an experimental group might be interested and do tests to see if it really works or not,” concludes the professor.
In vitro testing should soon take place, as the results of in-silico studies have shown to be promising and the research is being seen by many scientists around the world, being among the articles with the highest number of views in the Journal of Biomolecular Structure Dynamics in which it was published. Like countless other vegetables with healing properties, buriti is useful for many purposes and proven to be powerful in chemical testing. The rich flora of the Brazilian biomes can still hide several benefits for humanity that have not yet been explored, it is up to investment in science to be the driving force behind these discoveries.
