DAS181, a sialidase fusion protein, protects human airway epithelium against influenza virus infection: an in vitro pharmacodynamic analysis.

The Journal of Antimicrobial Chemotherapy
Gallen B Triana-BaltzerFang Fang

Abstract

The influenza virus (IFV) infection models commonly used to evaluate antiviral agents (e.g. MDCK cell line and mice) are limited by physiological differences from the human respiratory tract in vivo. Here we report the pharmacodynamics of DAS181, a sialidase fusion protein that inhibits influenza infection, in the model systems of well-defined human airway epithelium (HAE) culture and ex vivo culture of fresh human bronchial tissue, both of which are close mimics of the human respiratory tract in vivo. HAE culture and ex vivo human bronchi were used to evaluate the sialic acid removal and regeneration efficiency and IFV inhibition after various DAS181 treatment levels and regimens. DAS181 effectively desialylates HAE cultures and ex vivo bronchi tissues and therefore potently inhibits replication of different IFV strains. The treatment effect of DAS181 occurs immediately upon application to the epithelial surface and is unaffected by the respiratory mucus. In both HAE and human bronchial tissue, the inhibitory effect of DAS181 treatment lasts for at least 2 days. Approximately 80% epithelial surface desialylation and significant anti-IFV efficacy can be achieved at topical concentrations of DAS181 in the range of 5-10 microg/cm...Continue Reading

References

Apr 21, 1994·Journal of Theoretical Biology·G A Bocharov, A A Romanyukha
Nov 1, 1993·Immunobiology·T PeschkeD Gemsa
Dec 1, 1996·The Journal of Allergy and Clinical Immunology·S MatsukuraM Adachi
Feb 16, 2002·Methods : a Companion to Methods in Enzymology·K J Livak, T D Schmittgen
Jul 19, 2002·Seminars in Pediatric Infectious Diseases·Janet A Englund
Sep 10, 2003·International Reviews of Immunology·R Joel Lowy
Feb 14, 2004·Journal of Clinical Virology : the Official Publication of the Pan American Society for Clinical Virology·C L WardM Tisdale
Oct 28, 2004·Journal of Virology·Mikhail N MatrosovichHans-Dieter Klenk
Aug 17, 2005·FEMS Microbiology Reviews·Edward W A BrydonClive Sweet
Mar 24, 2006·Nature·Kyoko ShinyaYoshihiro Kawaoka
Mar 30, 2006·Antimicrobial Agents and Chemotherapy·Michael P MalakhovFang Fang
Jul 29, 2006·Journal of Virology·Catherine I ThompsonRaymond J Pickles
Jan 9, 2007·Nature Medicine·J M NichollsJ S M Peiris
Feb 3, 2007·Journal of Theoretical Biology·Baris HanciogluGilles Clermont
Mar 24, 2007·Journal of Theoretical Biology·David B Chang, Carl S Young
Aug 21, 2007·Journal of Medical Virology·Phillip Andrew Reece
Nov 17, 2007·The Journal of Infectious Diseases·Jessica A BelserJacqueline M Katz
Apr 1, 2008·Trends in Microbiology·John M NichollsJ S Malik Peiris
Apr 25, 2008·The Journal of Antimicrobial Chemotherapy·John M NichollsFang Fang
Sep 20, 2008·The Journal of Immunology : Official Journal of the American Association of Immunologists·Zhuqing LiRobert B Nussenblatt
Jul 15, 2009·Antimicrobial Agents and Chemotherapy·Renee W Y ChanJohn M Nicholls

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Citations

Nov 26, 2010·The Journal of Antimicrobial Chemotherapy·Gallen B Triana-BaltzerFang Fang
May 17, 2011·Toxicological Sciences : an Official Journal of the Society of Toxicology·Jeffrey L LarsonFang Fang
Oct 30, 2014·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·Roy F ChemalyMichael J Boeckh
Mar 24, 2012·Current Opinion in Virology·Michael G Ison
Sep 24, 2015·Antiviral Research·Jonathan M ZenilmanJ McLeod Griffiss
Feb 22, 2012·Transplant Infectious Disease : an Official Journal of the Transplantation Society·B B Guzmán-SuarezS Koo
Jul 10, 2012·Current Opinion in Immunology·Tracy HussellRobert J Snelgrove
May 29, 2015·Archives of Virology·Shashank TripathiSunil K Lal
Nov 6, 2013·FEMS Microbiology Reviews·Wander Van BreedamHans J Nauwynck
Apr 23, 2013·Antiviral Research·John M NichollsStuart M Haslam
Oct 19, 2013·Journal of Virological Methods·Xuefeng DengJianming Qiu
Feb 2, 2017·Influenza and Other Respiratory Viruses·Paulina KoszalkaAeron C Hurt
Jan 22, 2015·The Journal of Histochemistry and Cytochemistry : Official Journal of the Histochemistry Society·A Sally DavisJeffery K Taubenberger
Jul 10, 2010·Drugs·David A BoltzElena A Govorkova
Jun 21, 2019·Vaccines·Erasmus KoteyMunir Iqbal
Jul 24, 2018·Expert Opinion on Emerging Drugs·Marco ManteroMarta Di Pasquale
May 10, 2020·Current Oncology Reports·Rohit GosainMarc S Ernstoff
May 15, 2020·Clinical Microbiology Reviews·Naveen KumarBarry T Rouse
Aug 9, 2011·Expert Review of Anti-infective Therapy·Alexandra GodleeTao Dong
Sep 27, 2018·Frontiers in Immunology·Sophia Davidson
Mar 16, 2011·Alternatives to Laboratory Animals : ATLA·Kelly BérubéClaire Job
Jul 29, 2020·International Journal of Molecular Sciences·Rami A Al-HoraniKholoud F Aliter
Oct 29, 2020·ACS Infectious Diseases·Anil Mathew TharappelHongmin Li
Oct 13, 2020·Transplantation·Tina M Marinelli, Deepali Kumar
Aug 7, 2021·Critical Reviews in Microbiology·Fanhua WeiYujiong Wang
Oct 6, 2021·The Journal of Clinical Investigation·Alexander L GreningerAnne Moscona

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