Current approaches to dealing with a SARS-CoV-2 infection target the virus itself with antiviral drugs. But, 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, researchers found that all three branches of a three-pronged signaling 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 Nerea Irigoyen in the University of Cambridge, senior author of the report. "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%.
The next step is to test the treatment in mouse models. The scientists also want to see whether it works against other viruses, and illnesses such as pulmonary fibrosis and neurological disorders that also activate the UPR response in cells.
"We hope this discovery will enable the development a broad-spectrum anti-viral drug, effective in treating infections with other viruses as well as SARS-CoV-2. We've already found it has an effect on Zika virus too. It has the potential to have a huge impact," said Irigoyen.