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Anatomy of a molecule:
What makes remdesivir unique?

Experts weigh in on the chemistry of the potential SARS-nCoV-2 antiviral
Laurel Oldach
March 17, 2020

The World Health Organization in late January convened experts to discuss experimental therapeutics for patients with the emerging coronavirus with no name, no vaccine and no treatment. The panel reported that “among the different therapeutic options, remdesivir was considered the most promising candidate.”

Within weeks, a clinical trial of the compound was underway in China. Results are expected in April; in the meantime, the outbreak of SARS-nCoV-2, the virus that causes COVID-19, has become a global pandemic.

Remdesivir is a nucleoside analog, one of the oldest classes of antiviral drugs. It works by blocking the RNA polymerase that coronaviruses and related RNA viruses need to replicate their genomes and proliferate in the host body.

The molecule originally was synthesized as part of a screen for inhibitors of the hepatitis C virus RNA polymerase. Its inventors at Gilead Sciences decided to move forward with a different nucleoside analog compound to treat hepatitis C. But RNA-dependent RNA polymerases are conserved between many viruses. Experiments in vitro, in cell culture and in animal models have shown that remdesivir has broad-spectrum activity against RNA viruses, including filoviruses (like the one that causes Ebola) and coronaviruses.

Remdesivir resembles the RNA base adenosine, shown here as a monophosphate.

AMP.jpg

The compound and ATP have some important differences, but some features are very similar. ASBMB Today spoke to medicinal chemist Katherine Seley–Radtke at the University of Maryland, Baltimore County, and structural virologist Craig Cameron at the University of North Carolina, Chapel Hill about what makes the molecule interesting. Click on a feature marked in blue to read their remarks.

Laurel Oldach

Laurel Oldach is a science writer for the ASBMB.

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