联合疗法可保护猕猴免受马尔堡病毒病的侵袭。

Combination therapy protects macaques against advanced Marburg virus disease.

机构信息

Galveston National Laboratory, University of Texas Medical Branch, 301 University Blvd, Galveston, TX, USA.

Department of Microbiology and Immunology, University of Texas Medical Branch, 301 University Blvd, Galveston, TX, USA.

出版信息

Nat Commun. 2021 Mar 25;12(1):1891. doi: 10.1038/s41467-021-22132-0.

Abstract

Monoclonal antibodies (mAbs) and remdesivir, a small-molecule antiviral, are promising monotherapies for many viruses, including members of the genera Marburgvirus and Ebolavirus (family Filoviridae), and more recently, SARS-CoV-2. One of the major challenges of acute viral infections is the treatment of advanced disease. Thus, extending the window of therapeutic intervention is critical. Here, we explore the benefit of combination therapy with a mAb and remdesivir in a non-human primate model of Marburg virus (MARV) disease. While rhesus monkeys are protected against lethal infection when treatment with either a human mAb (MR186-YTE; 100%), or remdesivir (80%), is initiated 5 days post-inoculation (dpi) with MARV, no animals survive when either treatment is initiated alone beginning 6 dpi. However, by combining MR186-YTE with remdesivir beginning 6 dpi, significant protection (80%) is achieved, thereby extending the therapeutic window. These results suggest value in exploring combination therapy in patients presenting with advanced filovirus disease.

摘要

单克隆抗体 (mAbs) 和瑞德西韦是小分子抗病毒药物,对多种病毒具有治疗潜力,包括马尔堡病毒属和埃博拉病毒属 (丝状病毒科) 的成员,以及最近的 SARS-CoV-2。急性病毒感染的主要挑战之一是治疗晚期疾病。因此,延长治疗干预的窗口期至关重要。在这里,我们在马尔堡病毒 (MARV) 疾病的非人类灵长类动物模型中探索了 mAb 和瑞德西韦联合治疗的益处。当 rhesus 猕猴在接种 MARV 后 5 天 (dpi) 开始用 100%的人源 mAb (MR186-YTE) 或 80%的瑞德西韦治疗时,可以免受致死性感染,但如果从 6 dpi 开始单独用任一种药物治疗,则没有动物存活。然而,从 6 dpi 开始用 MR186-YTE 和瑞德西韦联合治疗,可显著提高保护率 (80%),从而延长治疗窗口期。这些结果表明,在出现晚期丝状病毒病的患者中探索联合治疗具有一定价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/05ae/7994808/f087563cf472/41467_2021_22132_Fig1_HTML.jpg

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