Oral administration of obeldesivir protects nonhuman primates against Sudan ebolavirus

Abstract

Obeldesivir (ODV, GS-5245) is an orally administered prodrug of the parent nucleoside of remdesivir (RDV) and is presently in phase 3 trials for COVID-19 treatment. In this work, we show that ODV and its circulating parent nucleoside metabolite, GS-441524, have similar in vitro antiviral activity against filoviruses, including Marburg virus, Ebola virus, and Sudan virus (SUDV). We also report that once-daily oral ODV treatment of cynomolgus monkeys for 10 days beginning 24 hours after SUDV exposure confers 100% protection against lethal infection. Transcriptomics data show that ODV treatment delayed the onset of inflammation and correlated with antigen presentation and lymphocyte activation. Our results offer promise for the further development of ODV to control outbreaks of filovirus disease more rapidly.

N-Substituted Pyrrole-Based Heterocycles as Broad-Spectrum Filoviral Entry Inhibitors

“…1 H NMR (400 MHz, CD 3 OD) δ 7.58 (d, J = 2.3 Hz, 1H), 7.41−7.16 (m, 5H), 6.88 (s, 1H), 6.43−6.38 (m, 1H), 5.71 (s, 2H). (31). To a solution of 4e (40.0 mg, 140 μmol) in dry DMF (3.00 mL/mmol) cooled to 0 °C, DIPEA (5.00 equiv, 701 μmol) and HATU (2.00 equiv, 280 μmol) were added sequentially.…”

“…25−27 Nucleoside analogues favipiravir, 28 brincidofovir, 29 and remdesivir 30 are the most advanced anti-EBOV small molecules to have been evaluated in clinical trials; however, the lack of efficacy or safety terminated their progression. More recent preclinical trials with obeldesivir resulted in 100% nonhuman primate protection against lethal SUDV, 31 which is promising for transcription-and replicationtargeting antifiloviral small molecules.…”