Coronavirus: Breakthrough trial of potent drug that ‘slipped under the radar’
Researchers at the Doherty Institute in Melbourne will trial a new treatment for coronavirus in a major clinical trial.
Researchers at the Doherty Institute in Melbourne will trial a new treatment for coronavirus in a major clinical trial, with hopes the repurposed drug nafamostat will prove a highly successful treatment for lung problems associated with COVID-19.
The drug is currently licensed for use in South Korea and Japan as a treatment for acute pancreatitis and some blood clotting conditions — but it has been shown in laboratory experiments to block SARS-CoV-2 from entering human cells.
Researchers said the drug appeared to be “far more potent” than remdesivir, which is used in some hospitals for the treatment of COVID-19. It will be tested on coronavirus patients as part of the ASCOT trial, which is being led by the Doherty Institute.
“Of all drugs with potency data from laboratory studies using human cell lines, nafamostat appears to be the most potent against SARS-CoV-2 and may be the only drug where blood concentrations almost always exceed levels required to stop the virus from replicating,” said Steven Tong, co-lead of clinical research at the Doherty Institute.
Professor Tong said that nafamostat was found to have action in blocking a protein called TMPRSS2 in human cells. “This TMPRSS2 is a critical protein that allows the SARS-CoV-2 virus to enter into human cells,” Professor Tong said.
The coronavirus’ spike protein binds to a receptor in the body called ACE-2 to attach to human cells. “What’s less well known is that this connection between ACE-2 and the spike protein needs to be cleaved for the virus to enter the cell. So, basically, the virus can attach to the ACE-2 receptor, and you need to cleave that connection to allow the virus to roll in and enter into the cell. This cleavage is done by the protein TMPRSS2. Nafamostat blocks the action of TMPRSS2, so this is a very potent effect in preventing the release of SARS-CoV-2 and its entry into the cell.
“Nafamostat has been found to be 100 times more potent than remdesivir,” Professor Tong said. “Of all the agents that we’ve considered bringing in to ASCOT, it was clearly the most potent.”
Other clinical trials are testing nafamostat given orally in the treatment of COVID-19, but the ASCOT trial will be the first to test the drug given intravenously.
“It’s one that seems to have slipped under the radar a little bit,” Professor Tong said.
The ASCOT trial has begun recruiting trial participants from India, given the difficulties of finding them in Australia due to the extremely low case numbers here.
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