晚期瑞德西韦治疗的启动部分保护了非洲绿猴免受致命的尼帕病毒感染。
Late remdesivir treatment initiation partially protects African green monkeys from lethal Nipah virus infection.
机构信息
Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
Laboratory of Virology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Hamilton, MT, USA.
出版信息
Antiviral Res. 2023 Aug;216:105658. doi: 10.1016/j.antiviral.2023.105658. Epub 2023 Jun 23.
Remdesivir is a nucleotide prodrug with preclinical efficacy against lethal Nipah virus infection in African green monkeys when administered 1 day post inoculation (dpi) (Lo et al., 2019). Here, we determined whether remdesivir treatment was still effective when treatment administration initiation was delayed until 3 dpi. Three groups of six African green monkeys were inoculated with a lethal dose of Nipah virus, genotype Bangladesh. On 3 dpi, one group received a loading dose of 10 mg/kg remdesivir followed by daily dosing with 5 mg/kg for 11 days, one group received 10 mg/kg on 12 consecutive days, and the remaining group received an equivalent volume of vehicle solution. Remdesivir treatment initiation on 3 dpi provided partial protection from severe Nipah virus disease that was dose dependent, with 67% of animals in the high dose group surviving the challenge. However, remdesivir treatment did not prevent clinical disease, and surviving animals showed histologic lesions in the brain. Thus, early administration seems critical for effective remdesivir treatment during Nipah virus infection.
瑞德西韦是一种核苷酸前药，在感染尼帕病毒的非洲绿猴中，在接种后 1 天（dpi）给药时具有临床前疗效（Lo 等人，2019 年）。在这里，我们确定了当治疗开始延迟到 3 dpi 时，瑞德西韦治疗是否仍然有效。三组六只非洲绿猴接种了致命剂量的尼帕病毒，基因型孟加拉国。在 3 dpi 时，一组接受 10 mg/kg 瑞德西韦的负荷剂量，然后每天给予 5 mg/kg，持续 11 天，一组连续 12 天给予 10 mg/kg，其余组给予等量的载体溶液。在 3 dpi 开始瑞德西韦治疗提供了部分保护，免受严重的尼帕病毒病，这是剂量依赖性的，高剂量组有 67%的动物存活下来。然而，瑞德西韦治疗并不能预防临床疾病，存活的动物在大脑中显示出组织学病变。因此，早期给药对于尼帕病毒感染期间瑞德西韦的有效治疗似乎至关重要。
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