Abstract
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 as a benchmark in current drug development efforts that will hopefully lead to orally available treatments to the benefit of a broader population.
【초록키워드】 Treatment, Antiviral, Remdesivir, animal model, antiviral effects, animal models, Antiviral effect, drug target, RNA-dependent RNA polymerase, small molecule, Viral RNA, RNA polymerase, mechanism of action, patients, mechanism, nucleotide, Proofreading, Template, viral RNA-dependent RNA polymerase, RNA synthesis, incorporation, effort, copy, RNA genome, cell cultures, active form, Delayed, benefit, viral load reduction, inhibited, provide, cause, expected, acting, infection with SARS-CoV-2, 【제목키워드】 Treatment, biochemical,