“The human protein is called PCNA [proliferating cell nuclear antigen] interacts with SARS-CoV-2 protein M [matrix], one of the molecules that make up the viral membrane and give it its shape. Fernando Moreira Simabuco, professor at UNICAMP’s School of Applied Sciences (FCA) in Limeira and principal investigator of the study, said: FAPESP.
The team used a range of techniques in vitro to investigate how the presence of the M virus protein in the organism causes PCNA, a protein involved in DNA repair, to migrate from the cell nucleus, where it commonly found, to the cytoplasm, a cell. region containing organelles responsible for important cellular functions.
According to the researchers, this migration suggests that viral and human proteins interact, a conclusion corroborated by other methods, such as the use of compounds to inhibit protein migration. from nucleus to cytoplasm. In cells treated with both a compound specific for PCNA and another compound that inhibited the movement of various proteins including PCNA, viral replication was reduced by 15% to 20% compared with other compounds. untreated cells.
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“If we were thinking about treating it, perhaps this reduction would be insignificant, but our main aim was to demonstrate the interaction and show it could be a therapeutic target,” said Simabuco. future.
In collaboration with researchers in the Department of Pathology of the USP School of Medicine, they analyzed lung tissue samples obtained during autopsies of deceased COVID-19 patients (see also: agencia. fapesp.br/32955/).
The expression of PCNA was found to be above normal in these samples, as did the expression of the protein gamaH2AX, a marker of DNA damage, reinforcing the results.
“This finding may point to another consequence of viral infection,” said Simabuco.
The first author of the paper was rika Pereira Zambalde, a postdoctoral researcher at FCA-UNICAMP under the supervision of Simabuco.
News about protein
The M protein is immobilized with the E and S proteins, in the membrane that envelopes SARS-CoV-2, and is the most abundant of its four main structural proteins, called structural because they form the shape. form for it. For this reason, it has been considered a potential target for drugs and vaccines.
S, the viral spike protein, is well known because it binds to the ACE receptor in human cells, a role that has made it the target of most current COVID-19 vaccines.
The human PCNA protein is studied extensively in the context of cancer research, for example in a project conducted by Simabuco at FCA-UNICAMP. However, little is known about the role of PCNA in viral infections.
Thus, the recently published paper offers a step forward to further investigate this interaction between SARS-CoV-2 and PCNA, facilitating the development of therapies. The next step will be to confirm the findings in animal models, although this is yet to be programmed.
Source: Eurekalert
