title: Modelling Ebola virus dynamics: Implications for therapy.
abstract: 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.
authors.affiliation: Centre for Vascular Research, University of New South Wales, Sydney, New South Wales, 2052, Australia.
authors.forename: Alexey
authors.initials: A
authors.lastname: Martyushev
authors.affiliation: Institute of Industrial Sciences, The University of Tokyo, Tokyo, 1538505, Japan.
authors.forename: Shinji
authors.initials: S
authors.lastname: Nakaoka
authors.affiliation: Laboratory of Viral Pathogenesis, Institute for Virus Research, Kyoto University, Kyoto, Kyoto, 6068507, Japan; CREST, JST, Kawaguchi, Saitama, 3320012, Japan.
authors.forename: Kei
authors.initials: K
authors.lastname: Sato
authors.affiliation: Laboratory of Ultrastructural Virology, Institute for Virus Research, Kyoto University, Kyoto, 6068507, Japan; CREST, JST, Kawaguchi, Saitama, 3320012, Japan; PRESTO, JST, Kawaguchi, Saitama, 3320012, Japan. Electronic address: t-noda@virus.kyoto-u.ac.jp.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Noda
authors.affiliation: Mathematical Biology Laboratory, Department of Biology, Faculty of Sciences, Kyushu University, Fukuoka, 8128581, Japan; PRESTO, JST, Kawaguchi, Saitama, 3320012, Japan; CREST, JST, Kawaguchi, Saitama, 3320012, Japan. Electronic address: siwami@kyushu-u.org.
authors.forename: Shingo
authors.initials: S
authors.lastname: Iwami
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000627:therapeutic use; D000998:Antiviral Agents / Q000009:adverse effects / Q000627:therapeutic use*; D004196:Disease Outbreaks; D029043:Ebolavirus / Q000502:physiology*; D019142:Hemorrhagic Fever, Ebola / Q000188:drug therapy* / Q000453:epidemiology / Q000821:virology*; D006801:Humans; D008390:Markov Chains; D008954:Models, Biological; D009010:Monte Carlo Method; D016896:Treatment Outcome; D014454:Uganda / Q000453:epidemiology; D019562:Viral Load; D014779:Virus Replication
chemical_list: D000911:Antibodies, Monoclonal; D000998:Antiviral Agents; C000594176:ZMapp
keywords: Ebola virus infection; Experimental treatment; Mathematical model; Virus dynamics