An article in Frontiers magazine reported in Cellular and infectious microbiology, according to a recent study by researchers
A recent study explained how a human protein interacts with the SARS-CoV-2 protein and described one of the ways the virus that causes Covid-19 disease recruits cells to reproduce.
In laboratory tests, researchers from the University of Campinas (UNICAP) and the University of São Paulo (USP) in Brazil inhibited the interaction of molecules with the drug, thereby reducing virus replication by 15-20%. They expect their results to contribute to the development of treatments for Covid-19.
Fernando Moreira Cimabuco, professor at the Unicamp School of Applied Sciences (FCA) in Limeira and lead author of a study supported by the Sao Paulo State Research Support Fund (FAPESP), notes: “A human protein known as PCNA (proliferating cell nucleus antigen) interacts with the M protein (“Microprotein matrix”) in SARS-CoV-2, which is one of the molecules that make up the membrane of the virus and give it shape. The discovery itself shows one of the ways in which a pathogen manipulates cellular function in order to continue its life cycle.”
The researchers used a number of methods in in vitro to study how the presence of viral M protein in the body causes PCNA, a protein involved in DNA repair, to migrate from the cell nucleus, where it normally resides, to the cell cytoplasm. a region of a cell containing organelles responsible for important cell functions.
According to the researchers, this migration is indicative of an interaction between human proteins and the virus, and this conclusion is supported by other methods, such as the use of compounds to prevent the transfer of proteins from the nucleus to the cytoplasm.
In cells treated with a certain PCNA compound and another compound that inhibits the migration of various proteins, including PCNA, viral replication was reduced by 15-20% compared to untreated cells.
“If we were considering treatment, this reduction might not be significant, but our main goal was to show the interaction and show that it could be a therapeutic target in the future,” Cimabuco said.
In collaboration with researchers in the Department of Pathology at the University of the South Pacific School of Medicine, they analyzed lung tissue samples obtained during autopsies of deceased Covid-19 patients.
The expression of PCNA in these samples was found to be higher than normal, as was the expression of gammaH2AX, a marker of DNA damage, confirming the results.
“This discovery may point to another consequence of being infected with the virus,” Chimabuko said.
The M protein, along with the E and S proteins, is anchored in the membrane surrounding SARS-CoV-2 and is the most abundant of the four major structural proteins and is called the skeletal proteins because they give it its shape. For this reason, it is considered a potential target for drugs and vaccines.
Notably, the viral spike protein (S) is well known as it binds to angiotensin-converting enzyme receptors in human cells, making it the target of most current Covid-19 vaccines.
The study of the human PCNA protein has taken place on a large scale in the context of cancer research, as evidenced by a project led by Cimabuco as part of a collaboration between Campinas State University and Unicamp School of Applied Sciences. However, little is known about the role of PCNA in viral infections. Thus, the recently published article offers a path for further research into this interaction between SARS-CoV-2 and PCNA, contributing to the development of therapeutic agents.
The next step will be to confirm the results in animal models, although this has not yet been programmed.