Today, the leading academic journal Cell magazine presents a large-scale study of the new coronavirus in the form of a cover paper. A multinational team found that when cells become infected with the new coronavirus, there are many significant changes. The researchers also found that some drugs could target these changes, potentially leading to the treatment of new coronavirus infections.
Blue cell silky pseudo-foot protrusions with orange sprouting virus particles (Image credits: Elizabeth Fischer, NIAID/NIH)
In the paper, the scientists point out that as a new class of coronaviruses, the new coronavirus has a “symptom-asymptomatic infection” that can be contagious before symptoms appear. We don’t know enough about how the virus can change when it infects cells.
To this end, the large team decided to use the mass spectrometry-based quantitative phosphoproteocs method to study whether the phosphorylation process within the cells affected by the infection of the common cell line. Phosphorylation is a key regulatory step of intracellular signaling pathways. Understanding how proteins from hosts and viruses are phosphorylationafter infection is expected to give us an idea of the pathology of the disease.
As the researchers expected, there was a significant increase in phosphorylation of many proteins at different points in time after the virus infected cells. This includes both proteins from the new coronavirus and host proteins that interact with the new coronavirus protein.
At different points in time after infection, the phosphorylation process of different proteins changes differently and is related to the viral cell cycle.
Based on the dynamics of these phosphorylation sites, the researchers further divided them into five different groups. Interestingly, each group can be hooked on the life cycle of the virus – the first group will rise within 2 hours of infection, associated with the virus entering the cell; the second group is related to replication and/or out-of-the-box (egress), the third fourth group is associated with RNA processing and will be downgraded, and the fifth group is related to the response to infection.
Specifically, after infection with the new coronavirus, CK2 and p38 MAPK will be activated, a variety of cytokines will also be produced, and eventually shut down and have fistapion-related kinases, leading to the cessation of the cell cycle. In addition, CK2 also promotes the production of fiopular pseudo-foot protrusions, which contain sprite particles. The moment was also recorded by scientists and became the cover of the magazine.
Illustration of the study.
What’s the use of understanding these changes in phosphorylation? Based on changes in the activity of the kinase responsible for phosphorylation and known drug action mechanisms, scientists have identified 87 different drugs and compounds that are potentially neo-coronavirus-infected drugs. Of these 87 molecules, 10 have been approved by the FDA and 53 are already in clinical trials.
The researchers tested the antiviral activity of 68 drugs and compounds and identified strong antiviral potential for CK2, p38 MAPK signaling pathways, PIKEYVE, and CDK inhibitors, making them potential targets for the future.