Concept

Intracellular processing of Remdesivir

  • Figure a shows the chemical structure of a 1′-CN modified adenosine C-nucleoside in blue (GS-441524) and Remdesivir; GS-441524 makes up the core of Remdesivir

  • Figure b shows the intracellular processing of Remdesivir. After diffusion into the cell, Remdesivir is metabolized into the nucleoside monophosphate via a series of steps that are believed to be triggered by esterase-mediated hydrolysis of the amino acid ester which in turn frees a carboxylate that cyclizes onto the phosophorus displacing the phenoxide. The reactive cyclic anhydride is hydrolysed by water to produce the alanine metabolite, whose P-N bond is hydrolysed by phosphoramidase-type enzymes to free the nucleoside monophosphate. The monophosphate then undergoes further phosphorylation events to produce the active nucleoside triphosphate, which is used by the viral RNA-dependent RNA polymerase (RdRp). RdRp uses the triphosphate to inhibit viral replication by inducing delayed chain termination.

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Updated 2020-07-22

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SARS-CoV-2 (COVID-19)

Biomedical Sciences