PMID- 12821466
OWN - NLM
STAT- MEDLINE
DCOM- 20030814
LR  - 20210526
IS  - 0066-4804 (Print)
IS  - 1098-6596 (Electronic)
IS  - 0066-4804 (Linking)
VI  - 47
IP  - 7
DP  - 2003 Jul
TI  - In vitro activities of benzimidazole D- and L-ribonucleosides against 
      herpesviruses.
PG  - 2186-92
AB  - Herpes simplex virus types 1 and 2 (HSV-1 and HSV-2), varicella-zoster virus 
      (VZV), cytomegalovirus (CMV), Epstein-Barr virus (EBV), human herpesvirus 6 
      (HHV-6), and human herpesvirus 8 (HHV-8) are responsible for a number of clinical 
      manifestations in both normal and immunocompromised individuals. The parent 
      benzimidazole ribonucleosides evaluated in this series, 
      2-bromo-5,6-dichloro-1-(beta-D-ribofuranosyl)benzimidazole (BDCRB) and maribavir 
      (1263W94), are potent and selective inhibitors of human CMV replication. These 
      nucleosides act by two different mechanisms. BDCRB blocks the processing and 
      maturation of viral DNA, whereas 1263W94 inhibits the viral enzyme pUL97 and 
      interferes with DNA synthesis. In the present study, we have evaluated the in 
      vitro antiviral activity of BDCRB, an analog, GW275175X (175X), and 1263W94 
      against the replication of HSV-1, HSV-2, VZV, CMV, EBV, HHV-6, and HHV-8. By 
      using various methodologies, significant activity was observed against human CMV 
      and EBV but not against HSV-1, HSV-2, VZV, HHV-6, or HHV-8. Plaque reduction 
      assays performed on a variety of laboratory and clinical isolates of human CMV 
      indicated that all strains, including those resistant to ganciclovir (GCV) and 
      foscarnet, were sensitive to all three benzimidazole ribonucleosides, with mean 
      50% effective concentration values of about 1 to 5 microM compared to that of GCV 
      at 6 microM. The toxicity of these compounds in tissue culture cells appeared to 
      be similar to that observed with GCV. These results demonstrate that the 
      benzimidazole ribonucleosides are active against human CMV and EBV and suggest 
      that they may be useful for the treatment of infections caused by these 
      herpesviruses.
FAU - Williams, Stephanie L
AU  - Williams SL
AD  - University of Alabama School of Medicine, Birmingham, Alabama 35233, USA.
FAU - Hartline, Caroll B
AU  - Hartline CB
FAU - Kushner, Nicole L
AU  - Kushner NL
FAU - Harden, Emma A
AU  - Harden EA
FAU - Bidanset, Deborah J
AU  - Bidanset DJ
FAU - Drach, John C
AU  - Drach JC
FAU - Townsend, Leroy B
AU  - Townsend LB
FAU - Underwood, Mark R
AU  - Underwood MR
FAU - Biron, Karen K
AU  - Biron KK
FAU - Kern, Earl R
AU  - Kern ER
LA  - eng
GR  - N01 AI085347/AI/NIAID NIH HHS/United States
GR  - 5-U19-AI46390/AI/NIAID NIH HHS/United States
GR  - N01-AI-85347/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Antimicrob Agents Chemother
JT  - Antimicrobial agents and chemotherapy
JID - 0315061
RN  - 0 (Antiviral Agents)
RN  - 0 (Benzimidazoles)
RN  - 0 (Ribonucleosides)
RN  - E24GX49LD8 (benzimidazole)
SB  - IM
MH  - Antiviral Agents/chemistry/*pharmacology
MH  - Benzimidazoles/chemistry/*pharmacology
MH  - Cytomegalovirus/drug effects/growth & development
MH  - Herpesvirus 1, Human/*drug effects/growth & development
MH  - Herpesvirus 2, Human/*drug effects/growth & development
MH  - Herpesvirus 3, Human/drug effects/growth & development
MH  - Herpesvirus 6, Human/drug effects/growth & development
MH  - Herpesvirus 8, Human/drug effects/growth & development
MH  - In Vitro Techniques
MH  - Ribonucleosides/chemistry/*pharmacology
MH  - Virus Replication/drug effects
PMC - PMC161863
EDAT- 2003/06/25 05:00
MHDA- 2003/08/15 05:00
PMCR- 2003/07/01
CRDT- 2003/06/25 05:00
PHST- 2003/06/25 05:00 [pubmed]
PHST- 2003/08/15 05:00 [medline]
PHST- 2003/06/25 05:00 [entrez]
PHST- 2003/07/01 00:00 [pmc-release]
AID - 1045 [pii]
AID - 10.1128/AAC.47.7.2186-2192.2003 [doi]
PST - ppublish
SO  - Antimicrob Agents Chemother. 2003 Jul;47(7):2186-92. doi: 
      10.1128/AAC.47.7.2186-2192.2003.