In a new study, researchers report how exactly an experimental antiviral drug stops coronaviruses.
Their study was published the same day that the National Institutes of Health announced that the drug in question, remdesivir, is being used in the nation’s first clinical trial of an experimental treatment for COVID-19, the illness caused by the SARS-CoV-2 virus.
The research was conducted by a team of academic and industry researchers.
All viruses have molecular machinery that copies their genetic material so that they can replicate.
Coronaviruses replicate by copying their genetic material using an enzyme known as the RNA-dependent RNA polymerase.
Until now, it has been difficult to get the polymerase complex that contains multiple proteins to work in a test tube.
Previous research in cell cultures and animal models has shown that remdesivir can block replication of a variety of coronaviruses, but until now it hasn’t been clear how it does so.
The research team studied the drug’s effects on the coronavirus that causes Middle East Respiratory Syndrome and reports that remdesivir blocks a particular enzyme that is required for viral replication.
They used polymerase enzymes from the coronavirus that causes MERS and found that the enzymes can incorporate remdesivir, which resembles an RNA building block, into new RNA strands.
Shortly after adding remdesivir, the enzyme stops being able to add more RNA subunits. This puts a stop to genome replication.
The scientists hypothesize that this might happen because RNA containing remdesivir takes on a strange shape that doesn’t fit into the enzyme.
To find out for certain, they would need to collect structural data on the enzyme and newly synthesized RNA.
Such data could also help researchers design future drugs to have even greater activity against the polymerase.
Remdesivir, which is manufactured by the American company Gilead Sciences, has not been approved as a drug anywhere in the world.
According to Gilead, results from a clinical trial with COVID-19 patients in China are expected in April.
The lead author of the study is Matthias Götte, a virologist and professor at the University of Alberta, Edmonton.
The study is published in the Journal of Biological Chemistry.
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