When a person is infected with SARS-CoV-2, the virus that causes COVID-19, it invades their cells and uses them to replicate - which puts the cells under stress. Current approaches to dealing with infection target the virus itself with antiviral drugs. But Cambridge scientists have switched focus to target the body’s cellular response to the virus instead.
In a new study, published in the journal PLOS Pathogens, they found that all three branches of a three-pronged signalling pathway called the ‘unfolded protein response’ (UPR) are activated in lab-grown cells infected with SARS-CoV-2. Inhibiting the UPR to restore normal cell function using drugs was also found to significantly reduce virus replication.
“The virus that causes COVID-19 activates a response in our cells - called the UPR - that enables it to replicate,” said Dr Nerea Irigoyen in the University of Cambridge’s Department of Pathology, senior author of the report.
She added: “Using drugs we were able to reverse the activation of this specific cellular pathway, and remarkably this reduced virus production inside the cells almost completely, which means the infection could not spread to other cells. This has exciting potential as an anti-viral strategy against SARS-CoV-2.”
Treatment with a drug that targets one prong of the UPR pathway had some effect in reducing virus replication. But treatment with two drugs together - called Ceapin-A7 and KIRA8 - to simultaneously target two prongs of the pathway reduced virus production in the cells by 99.5%. This is the first study to show that the combination of two drugs has a much greater effect on virus replication in cells than a single drug.
Image: Scanning electron microscope image of SARS-CoV-2 (orange) emerging from the surface of cells (green) cultured in the lab.
Credit: NIAID
Reproduced courtesy of the University of Cambridge