[Source: Los Alamos National Laboratories, full page: (LINK). Abstract, edited.]
LA-UR-16-28095 / Approved for public release; distribution is unlimited.
Title: Modeling Zika plasma viral dynamics in non-human primates: insights into viral pathogenesis and antiviral strategies
Author(s): Best, Katharine Guedj, Jeremie Madelain, Vincent de Lamballerie, Xavier L, So-Yonim Osuna, Christa E Whitney, James Perelson, Alan S.
Intended for: Proc Natl Acad Sci USA
- Modeling Zika plasma viral dynamics in non-human primates: insights into viral pathogenesis and antiviral strategies
- Katharine Best1, Jeremie Guedj2, Vincent Madelain2, Xavier de Lamballerie3, So-Yon Lim4,
- Christa E. Osuna4, James Whitney4, 5 and Alan S. Perelson1*
- 1Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545,
- USA; 2 IAME, UMR 1137, INSERM, Université Paris Diderot, Sorbonne Paris Cité Paris,
- France; 3 Université Aix Marseille, Institut de Recherche pour le Développement, École des
- Hautes Études en Santé Publique, EPV, Marseille, France; 4Center for Virology and Vaccine
- Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215,
- USA; 5Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA
- *Corresponding author; mailing address: MS-K710, Los Alamos National Laboratory, Los
- Alamos, NM 87545; telephone: 505-667-6829; fax: 505-665-3493; email: firstname.lastname@example.org
- Number of words:
- Text (including abstract, references, tables and figure legends):
- The recent outbreak of Zika virus (ZIKV) has been associated with fetal abnormalities and
- neurological complications, prompting global concern. Here we present the first mathematical
- analysis of the within-host dynamics of plasma ZIKV burden in a non-human primate model,
- allowing for characterization of the growth and clearance of ZIKV within an individual macaque.
- We find that the eclipse phase for ZIKV, the time between cell infection and viral production, is
- short (~4 hours), the median within-host basic reproductive number is approximately 9, and the
- lifetime of an infected cell while producing virus is about 6 hours. We also estimate that the
- average number of virions produced by an infected cell over its lifetime is ~6,000, although the
- assumed target cell density, 105/ml, influences this estimate. We also assessed the potential
- effect of an antiviral treatment that blocks viral replication, showing that the median time-to-
- undetectable plasma viral load (VL) can be reduced from 5 days to 3 days or less with a drug
- concentration ≥ 10 times the drug’s EC50 when treatment is given prophylactically starting at the
- time of infection. Treatment given ≥ 2 days post-infection is ineffective in reducing peak plasma
- VL or time to undetectable plasma VL. In the case of favipiravir, a polymerase inhibitor with
- activity against ZIKV, we predict a dose of 150 mg/kg given twice a day initiated at the time of
- infection can reduce the peak VL by approximately 3 logs and shortened the time to undetectable
- VL by about 3 days.
Keywords: Zika Virus; Antivirals; Favipiravir.