My good news contribution for today: Researchers in Denmark are starting to test a promising drug in #covid19 patients, barely a month after research appeared showing the drug could stop the virus in cell culture. Quick thread sciencemag.org/news/2020/04/t…
So let me briefly explain the strategies scientists are pursuing in the hope of saving #covid19 patients. The need is clear: For now, all we have are non-pharmaceutical interventions like #physicaldistancing. A vaccine is many months away at least. Drugs would be a huge help.
In order to fight the disease, doctors could try two things:
1. fight the virus and keep it from replicating
2. dampen the immune system, which may be responsible for much of the damage late in the disease.
In the end a combination of the two might be needed.
1. fight the virus and keep it from replicating
2. dampen the immune system, which may be responsible for much of the damage late in the disease.
In the end a combination of the two might be needed.
As Stanley Perlman told me: “If you knock down the virus without the host immune response, you may not change anything. If you knock down the host immune response without the virus, you can enhance virus replication, which would be a problem.”
But let’s look at strategy 1 here, fighting the virus. There are again two ways of doing this.
1a. attack the virus directly, i.e. block the proteins that the virus itself produces and uses. That is what drugs like remdesivir or kaletra are supposed to do.
1a. attack the virus directly, i.e. block the proteins that the virus itself produces and uses. That is what drugs like remdesivir or kaletra are supposed to do.
Or:
1b. Block something in us, the host. As Nevan Krogan (@KroganLab) told me: “The virus can’t live by itself, right? It needs our genes and proteins in order to live and to replicate.” So find something the virus needs (and we don’t desperately need) and block that.
1b. Block something in us, the host. As Nevan Krogan (@KroganLab) told me: “The virus can’t live by itself, right? It needs our genes and proteins in order to live and to replicate.” So find something the virus needs (and we don’t desperately need) and block that.
@KroganLab Scientists call these “host-directed therapies”. And the drug I’m highlighting in the story, camostat mesylate is an example. So what does it do?
@KroganLab Camostat mesylate binds to a protein on human cells called TMPRSS2. And SARS-CoV-2 needs this protein to efficiently enter human cells: The spike protein on top of the virus attaches to the ACE2 receptor on human cells. And then TMPRSS2 needs to make a cut in the spike. 
@KroganLab If TMPRSS2 doesn’t cleave the spike protein, then #SARSCoV2 cannot enter human cells efficiently. At least in cell culture. Researchers showed that with virus taken from a German patient and lung cells in the lab last month. cell.com/cell/pdf/S0092…
@KroganLab And because the drug is licensed in Japan, Danish researchers managed to put together a clinical trial at lightning speed and are planning to dose the first patients tomorrow. As with all these drugs, chances are it won’t work. But it’s another shot at making a difference!
