Researchers reveal new drug that can fight both cancer and Covid-19

A team of researchers at the Keck School of Medicine of USC has revealed that blocking the production of a chaperone protein could largely reduce the replication of SARS-CoV-2.

Though vaccination can protect against Covid-19, scientists continue to research ways to treat severe infections, notwithstanding people who cannot get vaccinated or if dangerous new strains of the virus arise and bypass vaccine protection.

Led by Amy S. Lee, Ph.D., professor of biochemistry and molecular medicine, the research team showed that a chaperone protein known as GRP78 plays a significant role in the spread of SARS-CoV-2. According to their study published in Nature Communications, blocking the production of GRP78 or hampering its activity with a new targeted drug stopped the Covid virus from replicating.

"A major problem in fighting SARS-CoV-2 is that it is constantly mutating and adapting itself to more efficiently infect and multiply in its host cells," Lee said in a statement. "If we keep chasing the virus around, this could become quite challenging and unpredictable."

Binding and inhibiting the activity of the GRP78 proved to be the key step

So, the researchers began exploring the role of GRP78 and found that while healthy cells require a fraction of GRP78 to function normally, cells under stress need more GRP78 to cope. In a 2021 paper, the researchers had shown that when SARS-CoV-2 enters the scene, "GRP78 is hijacked to work in tandem with other cellular receptors to bring the SARS-CoV-2 virus inside cells, where it can then reproduce and spread," as per the release. 

The team was doubtful if GRP78 was essential for the Covid virus to replicate inside human lung cells. When they examined human lung epithelial cells infected with SARS-CoV-2, they observed that as the viral infection intensifies, the infected cells produced higher levels of GRP78. 

So, Lee and her team decided to get a special messenger RNA tool in the ring to control the production of the GRP78 protein in human lung epithelial cells in cell culture, without interrupting other cellular processes. Afterward, when those cells were later infected with SARS-CoV-2, they produced a lower amount of the viral spike protein, thereby proving that GRP78 was essential for replication and production.

To further explore, the team also tested a recently identified small molecule drug, known as HA15, on the infected lung cells. Ha15 turned out to be successful against cancer cells, and in binding GRP78. 

HA15 and YUM70 can work against cancer cells and the Covid viral load

The researchers then tested HA15 in the body of genetically engineered mice infected with SARS-CoV-2 and found that the drug largely reduced viral load in the lungs. 

Along with HA15, Lee and her colleagues are also studying the GRP78 inhibitor, YUM70. They discovered that both HA15 and YUM70 can suppress the production of mutant KRAS proteins—a common mutation that tends to resist drug treatment—and reduce the viability of cancer cells bearing such mutations in pancreatic, lung, and colon cancer. Published in the journal Neoplasia, the findings suggest targeting GRP78 may help combat these deadly cancers.

Further research and clinical trials are required to prove that HA15 and YUM70 are safe and effective for use in humans.