Abstract
This study investigated the oral bioavailability and efficacy of BILS 45 BS, a selective herpes simplex virus (HSV) helicase-primase inhibitor, against acyclovir (ACV)-resistant (ACV(r)) infections mediated by the HSV type 1 (HSV-1) dlsptk and PAA(r)5 mutant strains. In vitro, the compound was more potent than ACV against wild-type clinical and laboratory HSV-1 strains and ACV(r) HSV isolates, as determined by a standard plaque reduction assay, with a mean 50% effective concentration of about 0.15 microM. The oral bioavailability of BILS 45 BS in hairless mice was 49%, with a peak concentration in plasma of 31.5 microM after administration of a single dose of 25 mg/kg. Following cutaneous infection of nude mice, both the HSV-1 dlsptk and PAA(r)5 mutant strains induced significant, reproducible, and persistent cutaneous lesions that lasted for more than 2 weeks. Oral treatment with ACV (100 or 125 mg/kg/day, three times a day by gavage) did not affect either mutant-induced infection. In contrast, BILS 45 BS at an oral dose of 100 mg/kg/day almost completely abolished cutaneous lesions mediated by both ACV(r) HSV-1 mutants. The 50% effective doses of BILS 45 BS were 56.7 and 61 mg/kg/day against dlsptk- and PAA(r)5-induced infect...Continue Reading
References
Aug 1, 1992·Antimicrobial Agents and Chemotherapy·P A Chatis, C S Crumpacker
Aug 22, 1991·The New England Journal of Medicine·S SafrinJ Mills
Sep 1, 1991·The Journal of General Virology·C R BrandtD R Grau
May 1, 1991·Antiviral Research·D M Coen
Apr 1, 1991·Antimicrobial Agents and Chemotherapy·E De Clercq, A Holý
Feb 1, 1989·Journal of Virology·E P Carmichael, S K Weller
Apr 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·J J CruteI R Lehman
Mar 1, 1989·Antimicrobial Agents and Chemotherapy·M N EllisD W Barry
Jun 1, 1989·Proceedings of the National Academy of Sciences of the United States of America·D M CoenD M Knipe
Dec 1, 1989·Annals of Internal Medicine·S L SacksD M Coen
Oct 1, 1989·Antimicrobial Agents and Chemotherapy·M N EllisT Spector
Aug 1, 1988·Journal of Virology·D J Goldstein, S K Weller
May 1, 1986·Antimicrobial Agents and Chemotherapy·B A Larder, G Darby
Dec 1, 1981·Journal of Virology·P A FurmanP A Schaffer
Apr 1, 1995·Antiviral Research·D W KimberlinR J Whitley
May 12, 1995·Journal of Medicinal Chemistry·J J CruteG E Wright
Jun 9, 1995·The Journal of Biological Chemistry·S DrachevaJ J Crute
Apr 1, 1994·Clinical Infectious Diseases : an Official Publication of the Infectious Diseases Society of America·R SnoeckE De Clercq
Sep 1, 1994·The Journal of Infectious Diseases·J P LalezariH S Jaffe
Jun 1, 1994·Journal of Virology·D K Klinedinst, M D Challberg
Feb 1, 1993·Pharmaceutical Research·T A ShepardP E Sparrow
Feb 7, 1997·The Journal of Biological Chemistry·S HealyM Dodson
Feb 14, 1997·The Journal of Biological Chemistry·K L Graves-WoodwardS K Weller
Jul 14, 1998·Antimicrobial Agents and Chemotherapy·J DuanM G Cordingley
Aug 8, 1998·Journal of Virology·F C SpectorM G Peterson
Oct 1, 1998·Antiviral Research·C Lawetz, M Liuzzi
Nov 12, 1998·Journal of the American Academy of Dermatology·E J Zabawski, C J Cockerell
Jan 3, 2001·American Journal of Kidney Diseases : the Official Journal of the National Kidney Foundation·M A Singer
Apr 3, 2002·Nature Medicine·James J CruteMichael G Cordingley
Citations
Apr 4, 2007·Archives of Virology·S BiswasH J Field
Nov 17, 2010·Antimicrobial Agents and Chemotherapy·Jocelyne Piret, Guy Boivin
Dec 24, 2013·Future Medicinal Chemistry·Subhajit BiswasHugh J Field
Jan 31, 2016·Antiviral Research·Marianne CollotSonia Burrel
Aug 13, 2013·Expert Opinion on Therapeutic Targets·Sandra K Weller, Robert D Kuchta
Aug 19, 2005·Expert Review of Anti-infective Therapy·Eric Denes, Sylvie Ranger-Rogez
Jul 9, 2014·Expert Opinion on Drug Discovery·Julia Hornig, Alistair McGregor
Mar 11, 2005·Expert Opinion on Investigational Drugs·Gerald Kleymann
Dec 2, 2004·Expert Opinion on Emerging Drugs·Arun ChakrabartyStephen K Tyring
Jun 10, 2008·Antiviral Research·Subhajit BiswasHugh J Field
Jun 17, 2008·British Journal of Pharmacology·C-Y Hsiang, T-Y Ho
Dec 23, 2011·British Journal of Haematology·Rob S Sellar, Karl S Peggs
Mar 31, 2016·International Journal of Oral Science·Yu-Chen JiangXiu-Rong Guo
Feb 12, 2015·Clinical Pharmacology and Therapeutics·S H JamesM N Prichard
Sep 8, 2004·Current Opinion in Pharmacology·Guy HewlettHelga Rübsamen-Waigmann
Jul 23, 2004·Antiviral Chemistry & Chemotherapy·Gerald Kleymann
Mar 16, 2007·Antiviral Chemistry & Chemotherapy·Subhajit BiswasHugh J Field
Jul 12, 2020·Virology Journal·Jun-Ting ChengHong-Wu Xin