Research novel coronavirus controls cell replication

The State University of Campinas (UNICAMP) and the University of So Paulo (USP) in Brazil conducted a study that demonstrates how a human protein interacts with a SARS-CoV-2 protein and one of the ways the virus that causes COVID-19 recruits cells to replicate, according to an article published in the journal “Frontiers in Cellular and Infection Microbiology.”

In laboratory testing, the scientists used a medication to impede the molecules’ interaction, lowering viral reproduction by 15% to 20%. They hope that their discoveries will contribute to the creation of COVID-19 therapeutics.

Human protein PCNA [proliferating cell nuclear antigen] interacts with SARS-CoV-2 protein M [matrix], one of the components that build up and provide structure to the virus’s membrane. Fernando Moreira Simabuco, a professor at UNICAMP’s School of Applied Sciences (FCA) in Limeira and the study’s lead author, said: “The discovery itself reveals one of the ways the virus manipulates cell function for its life cycle to occur.”

The researchers looked into how PCNA, a protein involved in DNA repair, migrates from the cell nucleus to the cytoplasm, an area of the cell containing organelles responsible for critical cell activities, when viral protein M is present in the organism.

The researchers claim that this migration shows how human and viral proteins interact, and additional techniques, such the use of substances to block protein migration from the nucleus to the cytoplasm, corroborate this claim. Viral replication was 15–20% lower in cells treated with a PCNA-specific chemical and another that inhibits the migration of several proteins, including PCNA, compared to untreated cells.
This reduction “may not have been significant if we were thinking about treatment,” Simabuco added. But the primary objective was to illustrate the relationship and indicate that it might serve as a future therapeutic target.
They examined lung tissue samples taken during the autopsies of COVID-19 patients who had passed away in partnership with scientists from the pathology department of the USP Medical School.

Both PCNA expression and the protein gamaH2AX, a DNA damage marker, were found to be greater than expected in these samples, corroborating the results.
Simabuco stated that this finding “may hint to yet another effect of viral infection.”
The most prevalent of the four key structural proteins that give SARS-CoV-2 its form is protein M, which is anchored in the membrane surrounding the virus together with proteins E and S. It has been identified as a possible target for drugs and vaccines as a result.
Since S, the viral spike protein, is well known for interacting to the ACE receptor in human cells, the majority of the available COVID-19 vaccines are designed to specifically target this protein.

A project run by Simabuco at FCA-UNICAMP demonstrates the breadth of research being done on the human protein PCNA in the field of cancer. But nothing is understood about PCNA’s function in viral infections.