According to the latest issue of Nature Communication, a new study by the Keck Medical Center of the University of Southern California in the United States shows that a chaperone protein called GRP78 plays a key role in the transmission of COVID-19. Studies also showed that blocking the production of GRP78 or inhibiting its activity with a new targeted drug could significantly reduce the replication of COVID-19. GRP78 is a key cell chaperone protein that helps regulate the folding of other cell proteins. In a paper in 2021, researchers from Keck Medical Center showed that when COVID-19 invaded, GRP78 was "hijacked" and operated with other cell receptors to bring the virus into the cell, and then replicate and spread there. This study has direct evidence that GRP78 is a proviral protein necessary for virus replication. The research team examined human lung epithelial cells infected with COVID-19, and observed that with the intensification of viral infection, infected cells produced higher levels of GRP78. Then, the researchers used a special messenger RNA tool to inhibit the production of GRP78 protein in human lung epithelial cells in cell culture without interrupting other cell processes. When these cells were later infected with COVID-19, they produced fewer viral spike proteins and released fewer viruses, which proved that GRP78 was necessary for virus replication and production. To further explore whether targeting GRP78 can treat COVID-19, researchers tested a recently discovered small molecule drug named HA15 on infected lung cells. This drug was developed to fight cancer cells, specifically binding GRP78 and inhibiting its activity. The study found that at a safe dose, this drug is very effective in reducing the number and size of COVID-19 plaques produced in infected cells, and has no harmful effect on normal cells. The researchers then tested HA15 in transgenic mice and found that the drug significantly reduced the load of COVID-19 in the lungs. The researchers said that these are the basic evidences of the principle study, and further studies such as clinical trials are needed. (Outlook New Times)
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