Late remdesivir treatment initiation partially protects African green monkeys from lethal Nipah virus infection

被引:4
|
作者
de Wit, Emmie [1 ]
Williamson, Brandi N. [1 ]
Feldmann, Friederike [2 ]
Goldin, Kerry [1 ]
Lo, Michael K. [3 ]
Okumura, Atsushi [1 ]
Lovaglio, Jamie [2 ]
Bunyan, Elaine [4 ]
Porter, Danielle P. [4 ]
Cihlar, Tomas [4 ]
Saturday, Greg [2 ]
Spiropoulou, Christina F. [3 ]
Feldmann, Heinz [1 ]
机构
[1] NIAID, NIH, Lab Virol, Hamilton, MT 59840 USA
[2] NIAID, NIH, Rocky Mt Vet Branch, Hamilton, MT USA
[3] CDCP, Atlanta, GA USA
[4] Gilead Sci, Foster City, CA USA
关键词
Nipah virus; Antiviral; Remdesivir; Nonhuman primate; Nucleotide analog; EBOLA-VIRUS;
D O I
10.1016/j.antiviral.2023.105658
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 chal-lenge. 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.
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页数:4
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