Remdesivir for the treatment of Covid-19: the value of biochemical studies

The nucleotide analogue prodrug remdesivir remains the only FDA-approved antiviral small molecule for the treatment of infection with SARS-CoV-2. Biochemical studies revealed that the active form of the drug targets the viral RNA-dependent RNA polymerase and causes delayed chain-termination. Delayed chain-termination is incomplete, but the continuation of RNA synthesis enables a partial escape from viral proofreading. Remdesivir becomes embedded in the copy of the RNA genome that later serves as a template. Incorporation of an incoming nucleotide triphosphate is now inhibited by the modified template. Knowledge on the mechanism of action matters. Enzymatic inhibition links to antiviral effects in cell cultures, animal models and viral load reduction in patients, which provides the logical chain that is expected for a direct acting antiviral. Hence, remdesivir also serves asa benchmark in current drug development efforts that will hopefully lead to orally available treatments to the benefit of a broader population.

Automated summary

Remdesivir is the only FDA-approved antiviral small molecule for treating SARS-CoV-2 infection, targeting the viral RNA-dependent RNA polymerase to inhibit viral replication. Its antiviral effects in cell cultures, animal models, and reduction of viral load in patients make it a benchmark for future drug development efforts aiming at orally available treatments.