Oral obeldesivir provides postexposure protection against Marburg virus in nonhuman primates

IF 58.7 1区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY Nature Medicine Pub Date : 2025-01-13 DOI:10.1038/s41591-025-03496-y
Robert W. Cross, Courtney Woolsey, Abhishek N. Prasad, Viktoriya Borisevich, Krystle N. Agans, Daniel J. Deer, Mack B. Harrison, Natalie S. Dobias, Karla A. Fenton, Tomas Cihlar, Anh-Quan Nguyen, Darius Babusis, Roy Bannister, Meghan S. Vermillion, Victor C. Chu, Thomas W. Geisbert
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Abstract

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.

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口服奥贝德西韦可在非人类灵长类动物中提供针对马尔堡病毒的暴露后保护
最近在卢旺达爆发的马尔堡病毒(MARV)疫情凸显了针对这种致死率高达 90% 的病原体采取有效对策的必要性。目前,还没有针对马尔堡病毒感染的疫苗或经批准的治疗方法,这与埃博拉等相关病毒不同。我们的研究表明,核苷类似物原药口服药物奥贝地韦(ODV)在体外对丝状病毒显示出良好的抗病毒活性,并在动物模型中提供显著的保护作用。在这项以猕猴(6只)为对象的研究中,暴露后24小时开始服用每日一次的ODV,为期10天的治疗方案可在千倍致死性MARV挑战中提供80%的保护,延缓病毒复制和发病。转录组分析表明,早期适应性反应与成功结果相关。与静脉注射抗病毒药物相比,ODV 等口服抗病毒药物在疫情爆发环境中具有后勤方面的优势,可以更方便地给药,覆盖更广泛的接触人群。我们的研究结果支持 ODV 作为丝状病毒的广谱口服暴露后预防药物的潜力。
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来源期刊
Nature Medicine
Nature Medicine 医学-生化与分子生物学
CiteScore
100.90
自引率
0.70%
发文量
525
审稿时长
1 months
期刊介绍: Nature Medicine is a monthly journal publishing original peer-reviewed research in all areas of medicine. The publication focuses on originality, timeliness, interdisciplinary interest, and the impact on improving human health. In addition to research articles, Nature Medicine also publishes commissioned content such as News, Reviews, and Perspectives. This content aims to provide context for the latest advances in translational and clinical research, reaching a wide audience of M.D. and Ph.D. readers. All editorial decisions for the journal are made by a team of full-time professional editors. Nature Medicine consider all types of clinical research, including: -Case-reports and small case series -Clinical trials, whether phase 1, 2, 3 or 4 -Observational studies -Meta-analyses -Biomarker studies -Public and global health studies Nature Medicine is also committed to facilitating communication between translational and clinical researchers. As such, we consider “hybrid” studies with preclinical and translational findings reported alongside data from clinical studies.
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