Oral obeldesivir provides postexposure protection against Marburg virus in nonhuman primates

The recent outbreak of Marburg virus (MARV) in Rwanda underscores the need for effective countermeasures against this highly fatal pathogen, with case fatality rates reaching 90%. Currently, no vaccines or approved treatments exist for MARV infection, distinguishing it from related viruses like Ebola. Our research demonstrates that the oral drug obeldesivir (ODV), a nucleoside analog prodrug, shows promising antiviral activity against filoviruses in vitro and offers significant protection in animal models. In this study with cynomolgus macaques (n=6), a 10-day regimen of once-daily ODV, initiated 24 hours post-exposure, provided 80% protection against a thousand-fold lethal MARV challenge, delaying viral replication and disease onset. Transcriptome analysis revealed that early adaptive responses correlated with successful outcomes. Compared to intravenous options, oral antivirals like ODV offer logistical advantages in outbreak settings, enabling easier administration and broader contact coverage. Our findings support ODV's potential as a broad-spectrum, oral postexposure prophylaxis for filoviruses.