There’s a lot of very cool immunology research being done right now in response to the COVID-19 pandemic. Anti-virals and vaccines top the list for many. But there are significant problems with each — anti-virals have not proven to be wonder drugs, offering only modest help for those already seriously ill, and an effective vaccine is still months or years away. Vaccines may have to be tailored to the age and immune status of various groups, just the way flu vaccines are. But there are other ways of thinking about minimizing both mortality (deaths) and morbidity (illnesses).
This is from Nevan Krogan, Professor and Director of Quantitative Biosciences Institute & Senior Investigator at the Gladstone Institutes, University of California, San Francisco
Kinases are proteins found in every cell of our body. There are 518 human kinases, and they act as major control hubs for virtually all processes in the body. They are able to add a small marker – a process called phosphorylation – to other proteins and thus change how, if and when a phosphorylated protein can do its work. Many cancers are caused by overactive kinases leading to uncontrolled cell growth, and drugs that slow kinases down can be highly effective at treating cancer.
Kinases are also fairly easy to target with drugs because of how they add phosphorylation markers to proteins. Researchers have developed a huge number of drugs, particularly cancer drugs, that work by essentially throwing a wrench into the mechanics of specific kinases in order to stop cell growth.
Viruses also change the function of cellular machinery – albeit on purpose – but instead of causing cell growth, the machinery is repurposed to produce more viruses. Not surprisingly, viruses take control over many kinases to do this.
It is impossible to actually see which kinases are activated at any time, but since each kinase can attach phosphorylation markers to only a few specific proteins, researchers can look at the phosphorylated proteins to determine what kinases are active at any time.
Some of the more interesting ones include Casein Kinase 2, which is involved in controlling how a cell is shaped. We also identified several kinases that work together in what is called the p38/MAPK signaling pathway. This pathway responds to and controls our body’s inflammation reaction. It is possible these kinases could be involved in the cytokine storm – a dangerous immune system overreaction – that some patients with severe COVID-19 experience.
While identifying the kinases involved in SARS-CoV-2 replication, we were also able to learn a lot about how the virus changes our bodies. For example, CK2 becomes much more active during the course of coronavirus infection and causes the growth of little tubes that extend from the surface of the cell. Under a microscope, it looks as if the cell has a full head of hair. We think SARS-CoV-2 might be using these long cell outgrowths – called filopodia – as viral highways to get new viruses closer to neighboring cells, thereby making infection easier.
There are 87 existing drugs that change the kinase-controlled pathways used by the coronavirus. Most of these drugs are already approved for human use or are currently in clinical trials to treat cancer, and could be quickly repurposed to treat COVID-19 patients.*
