An article published in a journal Frontiers of cellular and infectious microbiology reports a study by researchers from the State University of Campinas (UNICAMP) and the University of São Paulo (USP) in Brazil that shows how a human protein interacts with the SARS-CoV-2 protein and describes one of the ways the virus causes COVID- 19 recruits cells for replication.
U laboratory studies researchers inhibited the interaction between molecules with drugs and thereby reduced virus replication by 15–20%. They expect their findings to contribute to the development of treatments for COVID-19.
“A human protein known as PCNA [proliferating cell nuclear antigen] interacts with the SARS-CoV-2 M protein [matrix], one of the molecules that make up the virus membrane and give it its shape. The discovery itself reveals one way the pathogen manipulates cellular function life cycle continue,” said Fernando Moreiro Simabuku, a professor at the UNICAMP School of Applied Sciences (FCA) in Limeira and principal investigator of the study, which was supported by FAPESP.
The group used a series of in vitro techniques to investigate how the presence of the viral M protein in the body causes PCNA, a protein involved in DNA repair, to migrate from cell nucleus where it is normally found, in the cytoplasm, the region of the cell that contains the organelles responsible for important cell functions.
According to the researchers, this migration shows that the viral and human proteins interact, a finding supported by other methods, such as the use of compounds to inhibit the migration of proteins from the nucleus to the cytoplasm. In cells treated with both a PCNA-specific compound and another that inhibits the migration of various proteins, including PCNA, viral replication was reduced by 15% to 20% compared to untreated cells cells.
“If we were thinking about treatment, maybe this reduction wouldn’t be significant, but our main goal was to demonstrate the interaction and show that this could be a future therapeutic target,” Simabuka said.
In collaboration with researchers from the Department of Pathology at the USP School of Medicine, they analyzed lung tissue samples obtained during autopsies of deceased patients with COVID-19.
PCNA expression was higher than normal in these samples, as was gammaH2AX protein expression, a marker of DNA damage, supporting the findings.
“This finding may point to another consequence of being infected with the virus,” Simabuka said.
The first author of the paper is Erica Pereira Zambalde, a PhD student at FCA-UNICAMP under the supervision of Simabuk.
Protein news
The M protein is anchored along with the E and S proteins in the membrane that envelops SARS-CoV-2 and is the most common of the four main structural proteins, called structural because they give it its shape. For this reason, it has been considered a potential target for drugs and vaccines.
S, viral surge protein well known because it binds to the ACE receptor in human cells a role that has made it a target for most current COVID-19 vaccines.
The human protein PCNA is widely studied in the context of cancer research, as exemplified by the project conducted by Simabuka at FCA-UNICAMP. Little is known about the role of PCNA in viral infections however.
Thus, the newly published paper offers an avenue for further research into this interaction between SARS-CoV-2 and PCNA, contributing to the development of therapeutics. The next step will be to test the findings in animal models, although this is not yet planned.