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
相关论文
共 50 条
  • [41] UNRAVELING THE DYNAMICS OF EBOLA VIRUS WITH CONTACT TRACING AS CONTROL STRATEGY
    Andrawus, James
    Yusuf, Abdullahi
    Mustapha, Umar Tasiu
    Alshomrani, Ali S.
    Baleanu, Dumitru
    FRACTALS-COMPLEX GEOMETRY PATTERNS AND SCALING IN NATURE AND SOCIETY, 2023, 31 (10)
  • [42] Ebola virus disease: a review on epidemiology, symptoms, treatment and pathogenesis
    Goeijenbier, M.
    van Kampen, J. J. A.
    Reusken, C. B. E. M.
    Koopmans, M. P. G.
    van Gorp, E. C. M.
    NETHERLANDS JOURNAL OF MEDICINE, 2014, 72 (09) : 442 - 448
  • [43] The Drug Targets and Antiviral Molecules for Treatment of Ebola Virus Infection
    Wu, Wenjiao
    Liu, Shuwen
    CURRENT TOPICS IN MEDICINAL CHEMISTRY, 2017, 17 (03) : 361 - 370
  • [44] The Role of the Laboratory and Transfusion Service in the Management of Ebola Virus Disease
    Koepsell, Scott A.
    Winkler, Anne M.
    Roback, John D.
    TRANSFUSION MEDICINE REVIEWS, 2017, 31 (03) : 149 - 153
  • [45] How to treat Ebola virus infections? A lesson from the field
    Duraffour, Sophie
    Malvy, Denis
    Sissoko, Daouda
    CURRENT OPINION IN VIROLOGY, 2017, 24 : 9 - 15
  • [46] Structures of protective antibodies reveal sites of vulnerability on Ebola virus
    Murin, Charles D.
    Fusco, Marnie L.
    Bornholdt, Zachary A.
    Qiu, Xiangguo
    Olinger, Gene G.
    Zeitlin, Larry
    Kobinger, Gary P.
    Ward, Andrew B.
    Saphire, Erica Ollmann
    PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2014, 111 (48) : 17182 - 17187
  • [47] Ebola virus glycoprotein Fc fusion protein confers protection against lethal challenge in vaccinated mice
    Konduru, Krishnamurthy
    Bradfute, Steven B.
    Jacques, Jerome
    Manangeeswaran, Mohanraj
    Nakamura, Siham
    Morshed, Sufi
    Wood, Steven C.
    Bavari, Sina
    Kaplan, Gerardo G.
    VACCINE, 2011, 29 (16) : 2968 - 2977
  • [48] Ebola Virus Infection: Review of the Pharmacokinetic and Pharmacodynamic Properties of Drugs Considered for Testing in Human Efficacy Trials
    Madelain, Vincent
    Thi Huyen Tram Nguyen
    Olivo, Anaelle
    de Lamballerie, Xavier
    Guedj, Jeremie
    Taburet, Anne-Marie
    Mentre, France
    CLINICAL PHARMACOKINETICS, 2016, 55 (08) : 907 - 923
  • [49] The Use of TKM-100802 and Convalescent Plasma in 2 Patients With Ebola Virus Disease in the United States
    Kraft, Colleen S.
    Hewlett, Angela L.
    Koepsell, Scott
    Winkler, Anne M.
    Kratochvil, Christopher J.
    Larson, LuAnn
    Varkey, Jay B.
    Mehta, Aneesh K.
    Lyon, Marshall, III
    Friedman-Moraco, Rachel J.
    Marconi, Vincent C.
    Hill, Charles E.
    Sullivan, James N.
    Johnson, Daniel W.
    Lisco, Steven J.
    Mulligan, Mark J.
    Uyeki, Timothy M.
    McElroy, Anita K.
    Sealy, Tara
    Campbell, Shelley
    Spiropoulou, Christina
    Stroeher, Ute
    Crozier, Ian
    Sacra, Richard
    Connor, Michael J., Jr.
    Sueblinvong, Viranuj
    Franch, Harold A.
    Smith, Philip W.
    Ribner, Bruce S.
    CLINICAL INFECTIOUS DISEASES, 2015, 61 (04) : 496 - 502
  • [50] Predicting Ebola Severity: A Clinical Prioritization Score for Ebola Virus Disease
    Hartley, Mary-Anne
    Young, Alyssa
    Tran, Anh-Minh
    Okoni-Williams, Harry Henry
    Suma, Mohamed
    Mancuso, Brooke
    Al-Dikhari, Ahmed
    Faouzi, Mohamed
    PLOS NEGLECTED TROPICAL DISEASES, 2017, 11 (02):