Although vaccines against COVID-19 are effective, scientists continue to search for drugs to deal with possible new (and dangerous) strains of the virus. The latest discovery has been the GRP87 chaperone protein, essential for the spread of SARS-CoV-2.
The study, led by biochemist Amy S Leefrom the University of Southern California (USC) and published this Monday in Nature Communications, has discovered that this protein -implicated in the spread of other viruses- plays an essential role in the spread of the virus that causes COVID-19.
The study shows that when the production of GRP78 is blocked or its activity is inhibited with a new drug developed to treat cancer, the replication of the virus is greatly reduced.
Research suggests that this drug could protect against covid-19, and be effective even when new strains are developed.
“A major problem in the fight against SARS-CoV-2 is that it constantly mutates and adapts to infect and multiply more efficiently in its host cells,” explains Lee.
Seeking more stable ways to combat Covid-19, Lee and colleagues at USC Keck School of Medicine and Florida’s Cleveland Clinic Center for Research and Innovation began investigating the role of GRP78, a key cellular chaperone protein. .
In a study published in 2021, Keck researchers demonstrated that when SARS-CoV-2 infects an organism, GRP78 is hijacked to work in concert with other cellular receptors to deliver the SARS-CoV-2 virus into cells. where it reproduces and spreads.
But the researchers weren’t sure if GRP78 is “necessary and essential” for SARS-CoV-2 to replicate in human lung cells.
By examining human lung epithelial cells infected with SARS-CoV-2, the research team observed that as the viral infection intensifies, the infected cells produce higher levels of GRP78.
Then, in cell culture, Lee’s team suppressed GRP78 production in lung epithelial cells.
When cells were infected with SARS-CoV-2, they produced less of the viral spike protein and released much less of the virus to infect other cells, showing that GRP78 was necessary and essential for the virus to spread. retort.
Next, to test whether a GRP78 treatment is effective in treating covid, the team tested infected lung cells with the drug HA15, developed for use against cancer cells.
“We found that this drug was highly effective in reducing the number and size of SARS-CoV-2 plaques produced in infected cells, at safe doses that had no detrimental effect on normal cells,” explains Lee.
The researchers tested HA15 in genetically modified mice and found that the drug greatly reduced lung viral load.
In a parallel study, Lee and the Keck researchers, along with scientists from the University of Michigan, evaluated the efficacy of HA15 in cancer and of another GRP78 inhibitor, YUM70.
They found that 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 harboring such mutations in pancreatic, lung and colon cancer.
These findings, which have just been published in the journal Neoplasmsuggest that targeting GRP78 may help fight these deadly cancers.
These are basic proof-of-principle studies; Further research, including clinical trials, is needed to establish that HA15 and YUM70 are safe and effective for use in humans.
These and other GRP78 inhibitors are now being tested as treatments for both covid-19 and cancer.