April 19, 2020
Good morning MDIBL,
It’s late Sunday morning and I’ve been thinking about how life may be in what I would call “post-COVID-19 normal”. Once the restrictions are lifted (and we are all following the furious debates about rules and regulations at the moment) these new personal rules of hygiene and politeness will stay for quite a while. At MDIBL we have established our policy for employees, and we will stick to them as long as we need them. In addition to our rules for employees, we have to think about how to organize campus life once travel restrictions are lifted. We are discussing distancing in the dining hall, housing on campus, rules for seminars and regulations in the labs during courses. It is obvious that we will have smaller groups on campus and additional rules for them about how to behave to keep MDIBL a safe place.
But life is not only about rules and regulations. I have a fascinating new research project. Our research group works on glycocalyx, which are the sugar structures on the cell surface. We are investigating how proteins bind to these structures and how glycocalyx plays a role in cell signaling and cell activation. It turns out that coronaviruses bind first to glycocalyx before they bind to the ACE-2 receptor which helps the virus to enter the cells and infect them. Even more interesting, the virus binds to a specific family of glycocalyx molecules, the heparansulfates. These have been our pet molecules during the last few years. It seems that the virus needs at least two receptors to enter the cell; first binding to heparansulfates and then to ACE-2. This cooperative binding is essential for the virus to infect a cell.
During the past year we have developed small molecules to inhibit protein binding to heparansulfates. Our main interest was not the coronavirus but growth hormones like VEGF and FGF. However, we have worked with dozens of small molecules to find the most effective inhibitor. One of these molecules may prevent the virus from binding to the cell surface and prevent infection. We could apply these small inhibitory molecules with a spray. Perhaps before meeting somebody you use your COVID-19 spray and you may be protected against viruses entering your bronchial system. It is a promising hypothesis and we are writing a grant to investigate further.
This mechanism may be relevant for severely sick patients as well. In these patients we have observed microthrombi in the lung and a disturbance of their coagulation system. Heparins seem to work in these patients and heparins block the heparansulfate binding sites on endothelial cells (Njau and Haller, PLoS One, 2020;15(1):e0218494).
So, it seems there is not only life after COVID-19, there may be life with COVID-19.