Brazilian and foreign scientists will identify three possible composts for the treatment of Covid-19. These natural composts were selected in a triage with 500 drugs, which showed promise in inhibiting the PLpro protein – one of the enzymes responsible for the proliferation of SARS-CoV-2.
All three composts, 4-(2-hydroxyethyl)phenol (YRL), 4-hydroxybenzaldehyde (HBA) and methyl 3,4-dihydroxybenzoate (HE9) are derived from phenol and classified as polyphenols, a class of bioactive composts present in plants .
The research has the participation of specialists from the Unit for Drug Discovery laboratory of the Institute of Biomedical Sciences of the University of São Paulo (USP), and scholars from the University of Hamburg and the Deutsches Elektronen-Synchrotron (DESY), both from Germany.
published in magazine Communications Biology, the research suggests that the composts contain between 50% and 70% to the action of the enzyme. The testes formed in Vero cells (linhagem native to the rim of the macaque) and compared with a group of cells that did not receive the compost. A Vero linhagem possesses similarities with a human cell and was used as an experimental model in this type of study.
“As we insert the compounds into the infected cells, we found that they will prevent the replication of the coronavirus or reach PLpro, which has the ability to inactivate the cells of the immune system, which can lead to serious cases of damage. As a considerable percentage, two viruses were unable to replicate, the infectious viral particles were eliminated”, explains Edmarcia Elisa de Souza, post-doctoral fellow at USP.
“It is worth emphasizing that the composts do not present toxicity. Ou seja, we did not damage the integrity of the cells, mainly in the low concentrations in which the composts present antiviral activity”, he complements.
Novo alvo therapeutic
The discovery of the therapeutic approach is relevant, because it is an alternative to what we see as feito in science, according to the researchers.
“There is little in the literature about PLpro, so all new knowledge about it is important. Knowing that it is possible to inhibit the replication of SARS-CoV-2 by means of this protein is a great unknown, due to the majority of studies for treatments of Covid-19, such as the Spike and 3CL proteins. We managed to show that there are more options, if these studies have not advanced”, says Edmarcia.
The next step is to carry out tests on animal models to better assess the effectiveness of the three composts. Case sejam bem-sucesodos, it will be possible to advance to the clinical tests. “The composts forams isolated from nature, there is no record on their use as they are not in primary research and verified efficacy opens up possibilities for new therapies”, he states.
The leader of research in Brazil is Professor Carsten Wrenger, who receives support from the Fundação de Amparo à Pesquisa do Estado de São Paulo (Fapesp).
Selection of composts
Not total, six composts selected by the team of researchers from Germany were evaluated. “Our collaborators will observe the degree of interaction between the composts and PLpro. This was done by means of X-ray crystallography, an innovative method and still not widely used”, states Edmarcia.
Crystallography allows you to melt or compost protein and observe whether small crystals are produced together. Crystals are that they could not be seen in the light of two traditional microscopes. “By analyzing the crystals, we managed to produce three-dimensional models of the structures to identify if they are linked and where this happens. The more points of connection between them, the greater the affinity”, explains Professor Christian Betzel, leader of the study at the University of Hamburg, in Germany, and visiting professor at USP.
The efficacy of two three compounds against SARS-CoV-2 was subsequently analyzed in Vero cells infected with non-BSL3 Cell Culture Facility for Vector and Animal Research, Department of Parasitology of the Institute of Biomedical Sciences of USP. It is a biosafety level 3 laboratory (NB3), which confers protection to researchers who work with the cultivation of pathogenic microorganisms.
(With information from the Assessoria de Comunicação da USP).
Source: CNN Espanol