#Modeling #Zika #plasma viral #dynamics in non-human #primates: insights into viral #pathogenesis and #antiviral strategies (LANL, abstract)

[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

Issued: 2016-10-24

 

Abstract

1. Modeling Zika plasma viral dynamics in non-human primates: insights into viral pathogenesis and antiviral strategies
2. Katharine Best1, Jeremie Guedj2, Vincent Madelain2, Xavier de Lamballerie3, So-Yon Lim4,
3. Christa E. Osuna4, James Whitney4, 5 and Alan S. Perelson1*
4. 1Theoretical Biology and Biophysics, Los Alamos National Laboratory, Los Alamos, NM 87545,
5. USA; 2 IAME, UMR 1137, INSERM, Université Paris Diderot, Sorbonne Paris Cité Paris,
6. France; 3 Université Aix Marseille, Institut de Recherche pour le Développement, École des
7. Hautes Études en Santé Publique, EPV, Marseille, France; 4Center for Virology and Vaccine
8. Research, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02215,
9. USA; 5Ragon Institute of MGH, MIT, and Harvard, Cambridge, MA 02139, USA
10. …
11. *Corresponding author; mailing address: MS-K710, Los Alamos National Laboratory, Los
12. Alamos, NM 87545; telephone: 505-667-6829; fax: 505-665-3493; email: asp@lanl.gov
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14. Number of words:
15. Abstract:
16. Text (including abstract, references, tables and figure legends):
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18. Abstract
19. The recent outbreak of Zika virus (ZIKV) has been associated with fetal abnormalities and
20. neurological complications, prompting global concern. Here we present the first mathematical
21. analysis of the within-host dynamics of plasma ZIKV burden in a non-human primate model,
22. allowing for characterization of the growth and clearance of ZIKV within an individual macaque.
23. We find that the eclipse phase for ZIKV, the time between cell infection and viral production, is
24. short (~4 hours), the median within-host basic reproductive number is approximately 9, and the
25. lifetime of an infected cell while producing virus is about 6 hours. We also estimate that the
26. average number of virions produced by an infected cell over its lifetime is ~6,000, although the
27. assumed target cell density, 105/ml, influences this estimate. We also assessed the potential
28. effect of an antiviral treatment that blocks viral replication, showing that the median time-to-
29. undetectable plasma viral load (VL) can be reduced from 5 days to 3 days or less with a drug
30. concentration ≥ 10 times the drug’s EC50 when treatment is given prophylactically starting at the
31. time of infection. Treatment given ≥ 2 days post-infection is ineffective in reducing peak plasma
32. VL or time to undetectable plasma VL. In the case of favipiravir, a polymerase inhibitor with
33. activity against ZIKV, we predict a dose of 150 mg/kg given twice a day initiated at the time of
34. infection can reduce the peak VL by approximately 3 logs and shortened the time to undetectable
35. VL by about 3 days.

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Keywords: Zika Virus; Antivirals; Favipiravir.

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