A newly discovered drug that works against both covid-19 and cancer could prove to be a game-changer in medicine, scientists believe.
Researchers at the Keck School of Medicine of USC and the Cleveland Clinic Florida Research and Innovation Centre, found a vital protein GRP78, implicated in both covid-19 and cancer, could be countered with the drug named HA15. The drug specifically binds to GRP78 and inhibits its activity
The findings of the study were published in the journal Nature Communications.
GRP78 is a chaperone protein that, along with other cellular receptors, aids the entry of the SARS-COV-2 virus inside the cells, as per DrugTargetRveview. GRP78 has been implicated in the spread of other viruses as well.
The researchers, while examining infected human lung cells, found higher production of GRP78 in infected cells as the infection increased in intensity.
To determine the importance of GRP78 in the spread of Covid-19 infection, researchers suppressed the production of the protein in human lung epithelial cells in cell culture. When those cells were infected with the SARS-COV-2 virus, the study found that infected cells produced a lower amount of the viral spike protein and released much less of the virus to infect other cells.
“We now have direct evidence that GRP78 is a proviral protein that is essential for the virus to replicate,” co-author, Amy S. Lee, professor of biochemistry and molecular medicine at the Keck School of Medicine of USC, said, according to MedicalXpress.
Next, the research team tested the drug, HA15, on the infected lung cells to assess the feasibility of targeting GRP78 to bring down the infection.
“Lo and behold, we found that this drug was very effective in reducing the number and size of SARS-CoV-2 plaques produced in the infected cells, in safe doses which had no harmful effect on normal cells,” Lee commented.
After encouraging results, the researchers tested the efficacy of the drug in genetically-engineered mice, which were programmed to express a human SARS-CoV-2 receptor. The mice were infected with the SARS-COV-2 virus. The result was significantly reduced viral load in the lungs.
In another study, the research team at the Keck School of Medicine investigated the efficacy of HA15 in cancer, along with another GRP78 inhibitor YUM70. The study was conducted in collaboration with researchers at the University of Michigan, US.
It was found in the study that both, HA15 and YUM70, suppressed the production of mutant KRAS proteins, a common mutation that resists drug treatment, and also reduced the number of such mutant-bearing cancer cells.
Thus, the drugs could be used to target GRP78, which, in turn, would help fight off cancer.
The next step would be to test the safety and efficacy of the drug in humans through clinical trials.