Cross Robert W, Woolsey Courtney, Prasad Abhishek N, Borisevich Viktoriya, Agans Krystle N, Deer Daniel J, Harrison Mack B, Dobias Natalie S, Fenton Karla A, Cihlar Tomas, Nguyen Anh-Quan, Babusis Darius, Bannister Roy, Vermillion Meghan S, Chu Victor C, Geisbert Thomas W
Galveston National Laboratory, University of Texas Medical Branch, Galveston, TX, USA.
Department of Microbiology and Immunology, University of Texas Medical Branch, Galveston, TX, USA.
Nat Med. 2025 Apr;31(4):1303-1311. doi: 10.1038/s41591-025-03496-y. Epub 2025 Jan 13.
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 such as Ebola. Our study 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. Here with cynomolgus macaques (n = 6), a 10 day regimen of once-daily ODV, initiated 24 h after exposure, provided 80% protection against a thousandfold lethal MARV challenge, delaying viral replication and disease onset. Transcriptome analysis revealed that early adaptive responses correlated with successful outcomes. Compared with intravenous options, oral antivirals such as ODV offer logistical advantages in outbreak settings, enabling easier administration and broader contact coverage. Our findings support the potential of ODV as a broad-spectrum, oral postexposure prophylaxis for filoviruses.
最近在卢旺达爆发的马尔堡病毒（MARV）凸显了针对这种高致死性病原体采取有效应对措施的必要性，其病死率高达90%。目前，尚无针对马尔堡病毒感染的疫苗或获批治疗方法，这使其有别于埃博拉等相关病毒。我们的研究表明，口服药物奥贝德西韦（ODV），一种核苷类似物前药，在体外对丝状病毒显示出有前景的抗病毒活性，并在动物模型中提供显著保护。在此，对6只食蟹猴进行研究，在接触病毒24小时后开始为期10天的每日一次ODV给药方案，可提供80%的保护，抵御千倍致死剂量的马尔堡病毒攻击，延迟病毒复制和疾病发作。转录组分析显示，早期适应性反应与成功结果相关。与静脉给药选项相比，ODV等口服抗病毒药物在疫情爆发环境中具有后勤优势，便于给药且能覆盖更广泛的接触人群。我们的研究结果支持ODV作为丝状病毒广谱口服暴露后预防药物的潜力。
