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J Clin Virol. 2018 May;102:19-26. doi: 10.1016/j.jcv.2018.02.009. Epub 2018 Feb 15.

In vitro sensitivity of human parainfluenza 3 clinical isolates to ribavirin, favipiravir and zanamivir.

Author information

1
Division of Virology, Department of Pathology, University of Cambridge, Addenbrookes Hospital, Cambridge, United Kingdom; PHE - Public Health England Laboratory, Cambridge. Box 236, Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge, United Kingdom. Electronic address: aas31@cam.ac.uk.
2
Division of Virology, Department of Pathology, University of Cambridge, Addenbrookes Hospital, Cambridge, United Kingdom; Department of Bioengineering, 332 Mugar Life Science Building, 360 Huntington Ave, Northeastern University, Boston, MA, 02115-5000, USA.
3
Division of Virology, Department of Pathology, University of Cambridge, Addenbrookes Hospital, Cambridge, United Kingdom.
4
PHE - Public Health England Laboratory, Cambridge. Box 236, Cambridge University Hospitals NHS Foundation Trust, Hills Road, Cambridge, United Kingdom.

Abstract

BACKGROUND:

Human parainfluenza type 3 (HPIV3) is an important respiratory pathogen. Although a number of potential therapeutic candidates exist, there is currently no licensed therapy or vaccine. Ribavirin (RBV), favipiravir (FVP) and zanamivir (ZNV) are inhibitors with proven activity against influenza and with potential inhibitory activity against HPIV3 laboratory adapted strains in vitro.

OBJECTIVES:

To evaluate RBV, FVP and ZNV as inhibitors of minimally passaged UK clinical strains of HPIV3 as well as a laboratory adapted strain MK9 in vitro.

STUDY DESIGN:

The inhibitory action of RBV, FVP and ZNV was evaluated against nine minimally passaged clinical strains and a laboratory adapted strain MK9 using plaque reduction and growth curve inhibition in a cell culture model.

RESULTS:

Clinical isolates were found to be at least as susceptible as the laboratory adapted strains to RBV and FVP and significantly more susceptible to ZNV. However the inhibitory concentrations achieved by ZNV against clinical strains remain prohibitively high in vivo.

CONCLUSIONS:

RBV, FVP and ZNV were found to be effective inhibitors of HPIV3 in vitro. The lack of efficacy of RBV in vivo may be due to inability to reach required therapeutic levels. FVP, on the other hand, is a good potential therapeutic agent against HPIV3. Further studies using wild type clinical strains, as well as better formulation and delivery mechanisms may improve the utility of these three inhibitors.

KEYWORDS:

Clinical; Favipiravir; Parainfluenza; Ribavirin; Therapy; Zanamivir

PMID:
29477132
DOI:
10.1016/j.jcv.2018.02.009

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