Synthesis and antiviral activity of fatty acyl conjugates of remdesivir against severe acute respiratory syndrome coronavirus 2 and Ebola virus.

ABSTRACT: We report here the synthesis, purification, and characterization of mono- and di-fatty acyl conjugates of remdesivir (RDV) and their in vitro antiviral activity against SAR-CoV-2, an Ebola virus transcription- and replication-competent virus-like particle (trVLP) system, and infectious Ebola virus. The most potent monofatty acyl conjugate was 4b, containing a 4-oxatetradecanolyl at the 3' position. Monofatty acyl conjugates, 3'-O-tetradecanoyl (4a) (IC_50(VeroE6) = 2.3 μM; IC_50(Calu3) = 0.24 μM), 3'-O-4-oxatetradodecanoyl (4b) (IC_50(VeroE6) = 2.0 μM; IC_50(Calu3) = 0.18 μM), and 3'-O-(12-ethylthiododecanoyl) (4e) (IC_50(VeroE6) = 2.4 μM; IC_50(Calu3) = 0.25 μM) derivatives exhibited less activity than RDV (IC_50(VeroE6)

SUBMITTER: El-Sayed NS 

PROVIDER: S-EPMC8454092 | biostudies-literature | 2021 Dec

REPOSITORIES: biostudies-literature