TeachableMedicalNews article 05022020
Teachable moment in classrooms:
- cellular basis of life chapter – cell cycle and mitosis
- blood chapter – white blood cell types and their functions
- respiratory system chapter – alveoli as the sites of gas exchange
- respiratory system chapter – immune defense cells of alveoli
- lymphatic and immune system chapter – events of inflammation
How could the drug Opaganib help us defeat the SARS-CoV-2 coronavirus?
The news item: Recent articles reported that the investigational drug Opaganib will be evaluated as potential treatment of SARS-CoV-2 infected patients:
https://www.timesofisrael.com/2-israeli-covid-19-patients-improve-in-experimental-drug-trial/
The news item mentions that the drug has an anti-inflammatory effect, and that it is a sphingosine kinase inhibitor.
So, Why Do I Care?? Have you been living under a rock in the last few months??? The coronavirus, SARS-CoV-2, responsible for the COVID 19 disease has so far infected over 3.3 million people, and caused over 238,000 deaths worldwide (on the date of this article). The virus attacks the respiratory system, and may cause pneumonia and respiratory failure. The drug Opaganib holds promise as a possible treatment to lower the lethality of the virus.
Plain English, Please!!! First, let’s talk about what Opaganib is. This drug is used to fight some leukemias and inflammatory disorders where cells multiply out of control. So, this drug is not expected to kill the virus itself, but to prevent the lethal consequence of the SARS-CoV-2 infection, the cytokine storm.
Second, let’s talk about the cytokine storm. Our body reacts to viral infections with the process called inflammation. That defensive process includes immune system cells such as the white blood cells lymphocytes, neutrophils and monocytes that supposed to remove the virus from the site of infection, in our case the alveoli of the lungs. The white blood cells are stimulated to divide, and called to the inflamed alveoli. If we want to ask for help from friends, we send them a text, call them, or alert them on social media. For the immune system such a “call and stimulation” is done by the chemicals called cytokines. In some virus infected people large amounts of cytokines are made, a lot of white blood cells are created, and those cells release even more cytokines. This cloud of cytokines us called the cytokine storm. The large number of highly stimulated white blood cells damage small blood vessels, and fluids leak out and pool in the air sacs. That’s why shortness of breath develops, and ventilator machines are needed for the patients. The cytokine storm can damage blood vessels in the heart and kidneys as well.
Third, let’s talk about how Opaganib may help SARS-CoV-2 patients. To have a cytokine storm there needs to be great many white blood cells to create that storm. Inside our lymph nodes and other places white blood cells divide furiously to make that many white blood cells. So, one way to prevent a cytokine storm is to slow down cell division of those white blood cells. For cell division, mitosis, to happen, the cell has to pass through several molecular checkpoints that permit or deny the cell division. It’s like the cell gets a thumbs up or a thumbs down signal. One such checkpoint molecule is sphingosine; when it has a phosphate attached to it, it is a thumbs up, but when it is without a phosphate it is a thumbs down signal. Opaganib blocks the adding of phosphate to the sphingosine, so Opaganib creates many thumbs down signals for the mitosis. That leads to fewer white blood cells, that lowers the overall amount of cytokines, snuffs out the cytokine storm, and prevents deadly damage to the patient.
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