Complementary assays helping to overcome challenges for identifying neuraminidase inhibitors

Martina Richter; Lilia Schumann; Elisabeth Walther; Anja Hoffmann; Heike Braun; Ulrike Grienke; Judith M. Rollinger; Susanne von Grafenstein; Klaus R. Liedl; Johannes Kirchmair; Peter Wutzler; Andreas Sauerbrei; Michaela Schmidtke

doi:10.2217/FVL.14.97

Complementary assays helping to overcome challenges for identifying neuraminidase inhibitors

Martina Richter
, Lilia Schumann
, Elisabeth Walther
, Anja Hoffmann
, Heike Braun
, Ulrike Grienke
, Judith M. Rollinger
, Susanne von Grafenstein
, Klaus R. Liedl
, Johannes Kirchmair
, Peter Wutzler
, Andreas Sauerbrei
, Michaela Schmidtke

Publications: Contribution to journal › Article › Peer Reviewed

Abstract

Aims: In this study, we analyze the challenges involved in detecting novel neuraminidase inhibitors (NAIs) and offer strategies to overcome them with complementary bioassays. Materials & Methods: We investigated the inhibitory activities of NAIs (oseltamivir, zanamivir, DANA, katsumadain A and remazol) as well as non-NAIs (amantadine, nucleozin and rifampicin) on influenzaviral and bacterial (Streptococcus pneumoniae, Clostridium perfringens and Vibrio cholerae) neuraminidases (NAs) with chemiluminescence (CL)- and fluorescence (FL)-based assays. Furthermore, hemagglutination-based NA inhibition assays were established. Results: Our study shows three types of signal interference affecting the readout of biochemical assays: self-FL (katsumadain A and remazol), FL quenching (rifampicin) and CL quenching (rifampicin, remazol, nucleozin and katsumadain A). These challenges were overcome by hemagglutination-based assays. Conclusion: The latter allow a robust performance in discriminating NAIs and non-NAIs.

Original language	English
Pages (from-to)	77-88
Number of pages	12
Journal	Future Virology
Volume	10
Issue number	2
DOIs	https://doi.org/10.2217/FVL.14.97
Publication status	Published - 1 Feb 2015

Funding

This work was supported by the European Social Fund (ESF) and the Thuringian Ministry of Economy, Labour and Technology (TMWAT) with the project 'Optimization of influenza treatment by keeping into account secondary bacterial infections' (2011FGR0137) and by the Austrian Science Fund (FWF): projects 'Targeting Influenza Neuraminidase' (P23051) and 'Natural Lead Structures Targeting Influenza' (P24587). The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Austrian Fields of Science 2012

301209 Pharmacy

Keywords

assay interference
Clostridium perfringens
influenza virus
neuraminidase inhibition assay
neuraminidase inhibitors
self-fluorescence
signal quenching
Streptococcus pneumoniae
Vibrio cholerae
STREPTOCOCCUS-PNEUMONIAE
INFLUENZA-VIRUSES
HEMAGGLUTININ MUTATIONS
SUSCEPTIBILITY
H1N1
RESISTANCE
ZANAMIVIR

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10.2217/FVL.14.97

Cite this

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title = "Complementary assays helping to overcome challenges for identifying neuraminidase inhibitors",

abstract = "Aims: In this study, we analyze the challenges involved in detecting novel neuraminidase inhibitors (NAIs) and offer strategies to overcome them with complementary bioassays. Materials \& Methods: We investigated the inhibitory activities of NAIs (oseltamivir, zanamivir, DANA, katsumadain A and remazol) as well as non-NAIs (amantadine, nucleozin and rifampicin) on influenzaviral and bacterial (Streptococcus pneumoniae, Clostridium perfringens and Vibrio cholerae) neuraminidases (NAs) with chemiluminescence (CL)- and fluorescence (FL)-based assays. Furthermore, hemagglutination-based NA inhibition assays were established. Results: Our study shows three types of signal interference affecting the readout of biochemical assays: self-FL (katsumadain A and remazol), FL quenching (rifampicin) and CL quenching (rifampicin, remazol, nucleozin and katsumadain A). These challenges were overcome by hemagglutination-based assays. Conclusion: The latter allow a robust performance in discriminating NAIs and non-NAIs.",

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author = "Martina Richter and Lilia Schumann and Elisabeth Walther and Anja Hoffmann and Heike Braun and Ulrike Grienke and Rollinger, \{Judith M.\} and \{von Grafenstein\}, Susanne and Liedl, \{Klaus R.\} and Johannes Kirchmair and Peter Wutzler and Andreas Sauerbrei and Michaela Schmidtke",

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doi = "10.2217/FVL.14.97",

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AU - Richter, Martina

AU - Schumann, Lilia

AU - Walther, Elisabeth

AU - Hoffmann, Anja

AU - Braun, Heike

AU - Grienke, Ulrike

AU - Rollinger, Judith M.

AU - von Grafenstein, Susanne

AU - Liedl, Klaus R.

AU - Kirchmair, Johannes

AU - Wutzler, Peter

AU - Sauerbrei, Andreas

AU - Schmidtke, Michaela

PY - 2015/2/1

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AB - Aims: In this study, we analyze the challenges involved in detecting novel neuraminidase inhibitors (NAIs) and offer strategies to overcome them with complementary bioassays. Materials & Methods: We investigated the inhibitory activities of NAIs (oseltamivir, zanamivir, DANA, katsumadain A and remazol) as well as non-NAIs (amantadine, nucleozin and rifampicin) on influenzaviral and bacterial (Streptococcus pneumoniae, Clostridium perfringens and Vibrio cholerae) neuraminidases (NAs) with chemiluminescence (CL)- and fluorescence (FL)-based assays. Furthermore, hemagglutination-based NA inhibition assays were established. Results: Our study shows three types of signal interference affecting the readout of biochemical assays: self-FL (katsumadain A and remazol), FL quenching (rifampicin) and CL quenching (rifampicin, remazol, nucleozin and katsumadain A). These challenges were overcome by hemagglutination-based assays. Conclusion: The latter allow a robust performance in discriminating NAIs and non-NAIs.

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KW - RESISTANCE

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Complementary assays helping to overcome challenges for identifying neuraminidase inhibitors

Abstract

Funding

Austrian Fields of Science 2012

Keywords

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