These drugs don’t target the coronavirus—they target usIn another example of the blinding speed at which science is moving during the pandemic era, researchers at Aarhus University in Denmark will start a clinical trial of a drug named camostat mesylate tomorrow—barely 1 month after a Cell paper showed the compound can prevent the novel coronavirus, SARS-CoV-2, from entering human cells.
“If we are to have an impact on the rising epidemic, then we have to act right now,†says Ole Søgaard, the infectious disease physician leading the study.
One reason the Danish researchers can act so fast is that camostat mesylate is already licensed in Japan and South Korea to treat pancreatitis, a potentially fatal inflammation of the pancreas. Enough safety data were available to convince an ethical panel to greenlight the trial.
The trial also illustrates a new approach to combatting the virus. Thousands of researchers around the world are investigating existing drugs as potential therapies for COVID-19, most of them looking at antivirals, such as remdesivir, developed to treat Ebola, or Kaletra, a combination drug against HIV. But Nevan Krogan, a molecular biologist at the University of California, San Francisco, sees another opportunity: “The virus can’t live by itself, right? It needs our genes and proteins in order to live and to replicate.†Camostat mesylate is one of several candidate drugs that block those interactions. They don’t target the virus, but us, the host.
To identify these drugs, scientists study the complicated molecular dance that happens between a virus and its host cells. For instance, from past work, researchers know in detail how other coronaviruses—those that cause severe acute respiratory syndrome and Middle East respiratory syndrome—infect a cell. First, a protein on the viral surface called the spike attaches to a receptor on the human cell called ACE2. Then, another human protein, TMPRSS2, cleaves the spike protein, allowing the virus to fuse with the cell and start to replicate inside it. ..............
https://www.sciencemag.org/news/2020/04/these-drugs-don-t-target-coronavirus-they-target-us