In vitro sensitivity of human parainfluenza 3 clinical isolates to ribavirin, favipiravir and zanamivir.
Smielewska, Anna Alexandra
Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology
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Smielewska, A. A., Emmott, E., Goodfellow, I., & Jalal, H. (2018). In vitro sensitivity of human parainfluenza 3 clinical isolates to ribavirin, favipiravir and zanamivir.. Journal of clinical virology : the official publication of the Pan American Society for Clinical Virology, 102 19-26. https://doi.org/10.1016/j.jcv.2018.02.009
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.
Cell Line, Tumor, Humans, Parainfluenza Virus 3, Human, Respirovirus Infections, Amides, Pyrazines, Ribavirin, Antiviral Agents, Cytopathogenic Effect, Viral, Virus Replication, Zanamivir, Virus Attachment
This work was supported by Public Health England (PHE) PhD studentship fund 2013
Wellcome Trust (097997/Z/11/Z)
Public Health England (PHE) (PHE PhD Studentship Fund 2013)
External DOI: https://doi.org/10.1016/j.jcv.2018.02.009
This record's URL: https://www.repository.cam.ac.uk/handle/1810/275515