A study by researchers from the campus of the State University of Campinas (Unicamp) of Limeira (SP) and the University of São Paulo (USP) proved that the coronavirus manipulates human cells to be able to replicate inside people’s organisms. With the discovery, the study authors were able to reduce viral replication between 15% and 20% through the use of drugs.
Published in the journal Frontiers in Cellular and Infection Microbiology, the research described that a protein from the Covid-19 virus interacts with a human protein and recruits it.
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“The human protein known as PCNA [sigla para Proliferating Cell Nuclear Antigen] interacts with the M protein [matriz] of SARS-CoV-2, one of the molecules that make up the membrane of the virus and give it its shape. The discovery itself shows one of the ways in which the pathogen manipulates the cell’s function in order to follow its life cycle”, explains Fernando Moreira Simabuco, a professor at Unicamp’s Faculty of Applied Sciences (FCA), in Limeira, who coordinated the study. supported by Fapesp.
Using laboratory techniques, the group demonstrated that the presence of the virus M protein in the body causes PCNA to migrate from the cell nucleus – where it is normally found – to the cytoplasm, a region where the organelles, responsible for important cellular functions.
According to the researchers, this migration is one of the signs that the interaction between human cells and viruses is taking place. “In the organism without the infection, PCNA acts on DNA replication when cells divide and on DNA repair when damage occurs”, explains Érika Pereira Zambalde, author of the research and postdoctoral student at FCA-Unicamp.
In red, human PCNA protein migrates from the cell nucleus (in blue) to the cytoplasm in the presence of the M protein (green) — Photo: Orlando B. Scudero/ ICB-USP
Compost interferes with migration
After identifying the movement of cells, drugs were used to prevent the migration of proteins from the nucleus to the cytoplasm. According to the survey results, viral replication was lower after the use of the compounds.
“We observed that two drugs can reduce viral replication by about 15% to 20% in cell culture. This inhibition, considering therapy, may not yet be significant. However, the work shows that the search for drugs that can prevent this migration can indeed be an effective strategy in the treatment against Covid-19 and other viral diseases in the future”, explains Érika.
According to her, it is still not possible to stipulate the percentage of reduction in viral replication that must be achieved to conclude that the drug is effective against Covid-19.
“This is a difficult question, because we are working with cell culture, and when we extrapolate to the human body, we are talking about a very complex organism, with many interactions and cellular responses that we are not able to evaluate in the way that we do. [com células em laboratório]”, he explains.
Analysis of images captured under a microscope — Photo: Erika Zambalde/ Personal archive
As an example, she cites molnupiravir, a drug approved by the local federal agency for use in the United States in mild and moderate cases of Covid-19, reducing the rate of hospitalization and death by 6.8%, according to a clinical study in humans. “More studies are needed to confirm something similar to the drugs tested in our work,” she notes.
Autopsies on dead patients
In another stage of the study carried out by the postdoctoral student, in collaboration with researchers from the Department of Pathology of the Faculty of Medicine of USP, samples of lung tissue obtained during autopsies of patients who died by Covid-19 were also analyzed.
The results show that there was an increase in PCNA proteins and gammaH2AX, a protein that gives signs of DNA damage, which, according to the researchers, reinforces the results.
“This data may indicate another consequence of the coronavirus infection”, says Simabuco.
Costume used by researchers in the laboratory while working with the coronavirus — Photo: Erika Zambalde/ Personal archive
According to Erika, the next steps will be discover more details of how human cells are manipulated by the virus.
“Now, we intend to continue evaluating the interaction between PCNA and SARS-CoV-2 M protein in cell culture, to answer questions that were opened in this study and better understand the mechanisms by which this interaction is interfering with SARS replication. -CoV-2, and even possibly test new drugs in order to obtain a greater reduction in viral replication”, he detailed.
A study in animals or humans is also planned, but not in the short term, according to the researcher.