Modelling Ebola virus dynamics: Implications for therapy

被引:20
|
作者
Martyushev, Alexey [1 ]
Nakaoka, Shinji [2 ]
Sato, Kei [3 ,4 ]
Noda, Takeshi [4 ,5 ,7 ]
Iwami, Shingo [6 ,7 ]
机构
[1] Univ New South Wales, Ctr Vasc Res, Sydney, NSW 2052, Australia
[2] Univ Tokyo, Inst Ind Sci, Tokyo 1538505, Japan
[3] Kyoto Univ, Inst Virus Res, Lab Viral Pathogenesis, Kyoto, Kyoto 6068507, Japan
[4] JST, CREST, Kawaguchi, Saitama 3320012, Japan
[5] Kyoto Univ, Inst Virus Res, Lab Ultrastruct Virol, Kyoto 6068507, Japan
[6] Kyushu Univ, Fac Sci, Dept Biol, Math Biol Lab, Fukuoka 8128581, Japan
[7] JST, PRESTO, Kawaguchi, Saitama 3320012, Japan
基金
日本学术振兴会;
关键词
Ebola virus infection; Virus dynamics; Mathematical model; Experimental treatment; HEMORRHAGIC-FEVER; FILOVIRUS INFECTIONS; NONHUMAN-PRIMATES; POSTEXPOSURE PROTECTION; CONVALESCENT PLASMA; T-705; FAVIPIRAVIR; HEALTHY-ADULTS; HIV-INFECTION; MOUSE MODEL; VIRAL LOAD;
D O I
10.1016/j.antiviral.2016.10.004
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
Ebola virus (EBOV) causes a severe, often fatal Ebola virus disease (EVD), for which no approved antivirals exist. Recently, some promising anti-EBOV drugs, which are experimentally potent in animal models, have been developed. However, because the quantitative dynamics of EBOV replication in humans is uncertain, it remains unclear how much antiviral suppression of viral replication affects EVD outcome in patients. Here, we developed a novel mathematical model to quantitatively analyse human viral load data obtained during the 2000/01 Uganda EBOV outbreak and evaluated the effects of different antivirals. We found that nucleoside analogue- and siRNA-based therapies are effective if a therapy with a >50% inhibition rate is initiated within a few days post-symptom-onset. In contrast, antibody-based therapy requires not only a higher inhibition rate but also an earlier administration, especially for otherwise fatal cases. Our results demonstrate that an appropriate choice of EBOV-specific drugs is required for effective EVD treatment. (C) 2016 Elsevier B.V. All rights reserved.
引用
收藏
页码:62 / 73
页数:12
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