Modelling Ebola virus dynamics: Implications for therapy

Alexey Martyushev, Shinji Nakaoka, Kei Sato, Takeshi Noda, Shingo Iwami

Research output: Contribution to journalArticle

5 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)62-73
Number of pages12
JournalAntiviral Research
Volume135
DOIs
Publication statusPublished - Nov 1 2016

Fingerprint

Ebolavirus
Ebola Hemorrhagic Fever
Antiviral Agents
Therapeutics
Uganda
Virus Replication
Viral Load
Nucleosides
Pharmaceutical Preparations
Small Interfering RNA
Disease Outbreaks
Theoretical Models
Animal Models
Antibodies

All Science Journal Classification (ASJC) codes

  • Pharmacology
  • Virology

Cite this

Modelling Ebola virus dynamics : Implications for therapy. / Martyushev, Alexey; Nakaoka, Shinji; Sato, Kei; Noda, Takeshi; Iwami, Shingo.

In: Antiviral Research, Vol. 135, 01.11.2016, p. 62-73.

Research output: Contribution to journalArticle

Martyushev, Alexey ; Nakaoka, Shinji ; Sato, Kei ; Noda, Takeshi ; Iwami, Shingo. / Modelling Ebola virus dynamics : Implications for therapy. In: Antiviral Research. 2016 ; Vol. 135. pp. 62-73.
@article{d39f9364e0984cad93a570da93b90221,
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.",
author = "Alexey Martyushev and Shinji Nakaoka and Kei Sato and Takeshi Noda and Shingo Iwami",
year = "2016",
month = "11",
day = "1",
doi = "10.1016/j.antiviral.2016.10.004",
language = "English",
volume = "135",
pages = "62--73",
journal = "Antiviral Research",
issn = "0166-3542",
publisher = "Elsevier",

}

TY - JOUR

T1 - Modelling Ebola virus dynamics

T2 - Implications for therapy

AU - Martyushev, Alexey

AU - Nakaoka, Shinji

AU - Sato, Kei

AU - Noda, Takeshi

AU - Iwami, Shingo

PY - 2016/11/1

Y1 - 2016/11/1

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84991795273&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84991795273&partnerID=8YFLogxK

U2 - 10.1016/j.antiviral.2016.10.004

DO - 10.1016/j.antiviral.2016.10.004

M3 - Article

C2 - 27743917

AN - SCOPUS:84991795273

VL - 135

SP - 62

EP - 73

JO - Antiviral Research

JF - Antiviral Research

SN - 0166-3542

ER -