#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. *Corresponding author; mailing address: MS-K710, Los Alamos National Laboratory, Los
  11. Alamos, NM 87545; telephone: 505-667-6829; fax: 505-665-3493; email: asp@lanl.gov
  12. Number of words:
  13. Abstract:
  14. Text (including abstract, references, tables and figure legends):
  15. Abstract
  16. The recent outbreak of Zika virus (ZIKV) has been associated with fetal abnormalities and
  17. neurological complications, prompting global concern. Here we present the first mathematical
  18. analysis of the within-host dynamics of plasma ZIKV burden in a non-human primate model,
  19. allowing for characterization of the growth and clearance of ZIKV within an individual macaque.
  20. We find that the eclipse phase for ZIKV, the time between cell infection and viral production, is
  21. short (~4 hours), the median within-host basic reproductive number is approximately 9, and the
  22. lifetime of an infected cell while producing virus is about 6 hours. We also estimate that the
  23. average number of virions produced by an infected cell over its lifetime is ~6,000, although the
  24. assumed target cell density, 105/ml, influences this estimate. We also assessed the potential
  25. effect of an antiviral treatment that blocks viral replication, showing that the median time-to-
  26. undetectable plasma viral load (VL) can be reduced from 5 days to 3 days or less with a drug
  27. concentration ≥ 10 times the drug’s EC50 when treatment is given prophylactically starting at the
  28. time of infection. Treatment given ≥ 2 days post-infection is ineffective in reducing peak plasma
  29. VL or time to undetectable plasma VL. In the case of favipiravir, a polymerase inhibitor with
  30. activity against ZIKV, we predict a dose of 150 mg/kg given twice a day initiated at the time of
  31. infection can reduce the peak VL by approximately 3 logs and shortened the time to undetectable
  32. VL by about 3 days.

Keywords: Zika Virus; Antivirals; Favipiravir.

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Giuseppe Michieli

I am an Italian blogger, active since 2005 with main focus on emerging infectious diseases such as avian influenza, SARS, antibiotics resistance, and many other global Health issues. Other fields of interest are: climate change, global warming, geological and biological sciences. My activity consists mainly in collection and analysis of news, public services updates, confronting sources and making decision about what are the 'signals' of an impending crisis (an outbreak, for example). When a signal is detected, I follow traces during the entire course of an event. I started in 2005 my blog ''A TIME'S MEMORY'', now with more than 40,000 posts and 3 millions of web interactions. Subsequently I added an Italian Language blog, then discontinued because of very low traffic and interest. I contributed for seven years to a public forum (FluTrackers.com) in the midst of the Ebola epidemic in West Africa in 2014, I left the site to continue alone my data tracking job.