Optimizing celgosivir therapy in mouse models of dengue virus infection of serotypes 1 and 2: The search for a window for potential therapeutic efficacy

Antiviral Research
Satoru WatanabeSubhash G Vasudevan

Abstract

Although the antiviral drug celgosivir, an α-glucosidase I inhibitor, is highly protective when given twice daily to AG129 mice infected with dengue virus, a similar regimen of twice daily dosing did not significantly reduce serum viral loads in patients in a recent clinical trial. This failure presumably might reflect the initiation of treatment when patients were already viremic. To better mimic the clinical setting, we used viruses isolated from patients to develop new mouse models of DENV1 and DENV2 infection and employed the models to test the twice daily treatment, begun either on the day of infection or on the third day post-infection, when the mice had peak of viremia. We found that, although the treatment started on day 0 was effective on viral load reduction, it provided no benefit when begun on day 3, indicating that in vivo antiviral efficacy becomes less prominent once viremia reaches the peak level. To determine if the therapeutic regimen in humans could be improved, we tested regimen of four-times daily treatment and found that the treatment significantly reduced viremia, suggesting that a similar regimen may be effective in a human clinical trial. A new clinical trial to investigate an altered dosing regimen has...Continue Reading

References

Mar 14, 2000·Journal of Virological Methods·H H HoungN Kanesa-thasan
Nov 18, 2009·Proceedings of the National Academy of Sciences of the United States of America·Zheng YinPei-Yong Shi
Apr 13, 2012·The New England Journal of Medicine·Cameron P SimmonsBridget Wills
Jul 19, 2012·The Journal of Infectious Diseases·Nguyet Minh NguyenCameron P Simmons
Feb 5, 2013·Antiviral Research·Stuart T PerrySujan Shresta
Oct 15, 2014·Antimicrobial Agents and Chemotherapy·Margot CarocciPriscilla L Yang

❮ Previous
Next ❯

Citations

Feb 14, 2016·Antiviral Research·Margot Carocci, Priscilla L Yang
Jun 1, 2016·International Journal of Biomaterials·Romina CrociClaudio Nastruzzi
Jul 13, 2016·Expert Opinion on Drug Discovery·Huda MakhlufSujan Shresta
Aug 29, 2016·Antiviral Research·Verónica M QuintanaViviana Castilla
Sep 21, 2016·Current Opinion in Virology·Eliana G Acosta, Ralf Bartenschlager
Sep 27, 2016·Antiviral Research·Mariano A Garcia-BlancoChristopher Nicchitta
Jan 21, 2017·Biochemical Pharmacology·Jenn-Haung LaiShie-Liang Hsieh
Apr 15, 2017·Biochemical Society Transactions·Dominic S AlonziNicole Zitzmann
Aug 8, 2018·The Journal of Infectious Diseases·Satoru WatanabeSubhash G Vasudevan
Feb 13, 2018·Nature Reviews. Microbiology·Christopher J NeufeldtRalf Bartenschlager
Sep 28, 2017·The Journal of General Virology·Gregg N MilliganNigel Bourne
Jul 3, 2019·The Journal of Clinical Investigation·Abhay Ps RathoreAshley L St John
Jun 9, 2020·Biochemical Society Transactions·Spencer J Williams, Ethan D Goddard-Borger
Mar 22, 2018·Scientific Reports·Vanessa V SarathyAlan D T Barrett
May 6, 2017·Nature Reviews. Drug Discovery·Veaceslav BoldescuChristian D Klein
Nov 30, 2018·Frontiers in Cellular and Infection Microbiology·Mohammad Khalid ZakariaAlessandro Marcello
Dec 7, 2018·BMC Complementary and Alternative Medicine·Mohd Ridzuan Mohd Abd RazakAmi Fazlin Syed Mohamed
Apr 13, 2019·Glycobiology·Sarah O'KeefeStephen High
Apr 14, 2017·The Journal of Infectious Diseases·Jenny G H LowSubhash G Vasudevan
Feb 6, 2020·Expert Opinion on Drug Discovery·Alessandro SinigagliaLuisa Barzon
Sep 29, 2020·Glycobiology·Elizabeth C ClarkeSteven B Bradfute
Aug 10, 2020·Antiviral Research·Lisa Evans DeWaldKelly L Warfield
Jul 24, 2021·European Journal of Medicinal Chemistry·Crystall SwarbrickGerasimos Rassias

❮ Previous
Next ❯

Related Concepts

Related Feeds

Antivirals

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.

Antivirals (ASM)

Antivirals are medications that are used specifically for treating viral infections. Discover the latest research on antivirals here.