Ebola virus dynamics in mice treated with favipiravir.
The polymerase inhibitor favipiravir is a candidate for the treatment of Ebola virus disease. Here, we designed a mathematical model to characterize the viral dynamics in 20 mice experimentally infected with Ebola virus, which were either left untreated or treated with favipiravir at 6 or 8days post infection. This approach provided estimates of kinetic parameters of Ebola virus reproduction, such as the half-life of productively infected cells, of about 6h, and the basic reproductive number which indicates that virus produced by a single infected cell productively infects about 9 new cells. Furthermore, the model predicted that favipiravir efficiently blocks viral production, reaching an antiviral effectiveness of 95% and 99.6% at 2 and 6days after initiation of treatment, respectively. The model could be particularly helpful to guide future studies evaluating favipiravir in larger animals.
INSERM, IAME, UMR 1137, F-75018 Paris, France; Université Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, F-75018 Paris, France.
Vincent
V
Madelain
Bernhard-Nocht-Institute for Tropical Medicine, 20359 Hamburg, Germany; German Centre for Infection Research (DZIF), Partner Site Hamburg, Germany.
Lisa
L
Oestereich
Center for Modeling and Simulation in the Biosciences, BioQuant-Center, Heidelberg University, 69120 Heidelberg, Germany.
Frederik
F
Graw
INSERM, IAME, UMR 1137, F-75018 Paris, France; Université Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, F-75018 Paris, France.
Thi Huyen Tram
TH
Nguyen
Aix Marseille Université, IRD French Institute of Research for Development, EHESP French School of Public Health, EPV UMR_D 190 "Emergence des Pathologies Virales", F-13385 Marseille, France; Institut Hospitalo-Universitaire Méditerranée Infection, F-13385 Marseille, France.
Xavier
X
de Lamballerie
INSERM, IAME, UMR 1137, F-75018 Paris, France; Université Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, F-75018 Paris, France.
France
F
Mentré
Bernhard-Nocht-Institute for Tropical Medicine, 20359 Hamburg, Germany; German Centre for Infection Research (DZIF), Partner Site Hamburg, Germany.
Stephan
S
Günther
INSERM, IAME, UMR 1137, F-75018 Paris, France; Université Paris Diderot, IAME, UMR 1137, Sorbonne Paris Cité, F-75018 Paris, France. Electronic address: jeremie.guedj@inserm.fr.
Jeremie
J
Guedj
D000577:Amides / Q000008:administration & dosage*; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage*; D004195:Disease Models, Animal; D029043:Ebolavirus / Q000254:growth & development* / Q000302:isolation & purification; D005260:Female; D019142:Hemorrhagic Fever, Ebola / Q000188:drug therapy* / Q000821:virology*; D008810:Mice, Inbred C57BL; D008962:Models, Theoretical; D011719:Pyrazines / Q000008:administration & dosage*; D016019:Survival Analysis; D019562:Viral Load
D000577:Amides; D000998:Antiviral Agents; D011719:Pyrazines; C462182:favipiravir
Ebola; Favipiravir; Modeling; Viral kinetics