Researchers have demonstrated how the drug
known as remdesivir works, presenting the viral RNA polymerase of coronaviruses
as a target for these conditions.
A team of academic and industry researchers
has reported new findings on how exactly an investigational antiviral drug
stops coronaviruses. The paper was published the same day that the US National
Institutes of Health (NIH) announced that the drug in question, remdesivir, is
being used in the country’s first clinical trial of an experimental treatment
for COVID-19, the illness caused by the SARS-CoV-2 virus.
Previous research in cell cultures and animal
models has shown that remdesivir can block replication of a variety of coronaviruses,
but until now it has not been clear how it does so. The researchers, from the
University of Alberta, US, and Gilead, studied the drug’s effects on the
coronavirus that causes Middle East Respiratory Syndrome (MERS). They found
that remdesivir blocks a particular enzyme that is required for viral
replication.
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.
“It hasn’t been easy to work with these viral
polymerases,†Matthias Götte, a virologist and professor at the University of
Alberta who led the study. He explained that this has slowed research into new
drugs’ function.
Using polymerase enzymes from the coronavirus
that causes MERS, scientists in Götte’s lab 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 halts genome replication.
The scientists hypothesise that this might
happen because RNA containing remdesivir takes on a strange shape that does not
fit into the enzyme. To find out for certain, they would need to collect
structural data on the enzyme and newly synthesised RNA. Such data could also
help researchers design future drugs to have even greater activity against the
polymerase. They suggest the viral RNA polymerase of coronaviruses as a target.
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