A Chemoenzymatic Synthesis of the (R_P)-Isomer of the Antiviral Prodrug Remdesivir.

ABSTRACT: The COVID-19 pandemic threatens to overwhelm healthcare systems around the world. The only current FDA-approved treatment, which directly targets the virus, is the ProTide prodrug remdesivir. In its activated form, remdesivir prevents viral replication by inhibiting the essential RNA-dependent RNA polymerase. Like other ProTide prodrugs, remdesivir contains a chiral phosphorus center. The initial selection of the (S_P)-diastereomer for remdesivir was reportedly due to the difficulty in producing the pure (R_P)-diastereomer of the required precursor. However, the two currently known enzymes responsible for the initial activation step of remdesivir are each stereoselective and show differential tissue distribution. Given the ability of the COVID-19 virus to

SUBMITTER: Bigley AN 

PROVIDER: S-EPMC7418565 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature