PMID- 12719005
OWN - NLM
STAT- MEDLINE
DCOM- 20030812
LR  - 20191210
IS  - 0166-3542 (Print)
IS  - 0166-3542 (Linking)
VI  - 58
IP  - 1
DP  - 2003 Mar
TI  - Inhibition of HSV-1 replication and reactivation by the mutation-insensitive 
      transcription inhibitor tetra-O-glycyl-nordihydroguaiaretic acid.
PG  - 35-45
AB  - Methylated derivatives of nordihydroguaiaretic acid (NDGA)were previously shown 
      to be potent mutation-resistant inhibitors of herpes simplex virus type 1 (HSV-1) 
      which target Sp1 protein binding to critical viral promoters. The hydrophobic 
      nature of these agents, however, renders them relatively water-insoluble and, 
      therefore, limits their applicability. We report here on the anti-HSV-1 
      properties of a related but water-soluble glycylated derivative of NDGA, 
      tetra-O-glycyl-NDGA (G(4)N). In yield reduction assays, G(4)N inhibited 
      replication of laboratory and clinical strains of wild type HSV-1 and 
      ACV-resistant (HSV-1(R)) strains of HSV-1 in a dose-dependent manner, with 
      average IC(50) values of 4.7 and 3.2 microM against wild-type and HSV-1(R) 
      strains, respectively. An MTT-based cytotoxicity assay revealed a TC(50) value of 
      73.2 microM for G(4)N on Vero cells, with no reduction in viability detected at 
      concentrations below 30 microM. Similar to its methylated counterparts, G(4)N was 
      found to inhibit transcription of the HSV-1 ICP4 gene, a major immediate early 
      viral regulator, and gel mobility shift assays showed it can block Sp1 protein 
      binding to cognate sites on the ICP4 promoter. In anticipation of its potential 
      use as a systemic anti-HSV-1 agent, we tested G(4)N in a murine trigeminal 
      ganglia (TG) explant model system, and found G(4)N was able to prevent HSV-1 
      reactivation from explanted and cultured latently infected TG.
FAU - Park, Richard
AU  - Park R
AD  - Department of Biology, The Johns Hopkins University, Baltimore, MD 21218, USA.
FAU - Giza, Paul E
AU  - Giza PE
FAU - Mold, David E
AU  - Mold DE
FAU - Huang, Ru Chih C
AU  - Huang RC
LA  - eng
GR  - 1R01DE12165/DE/NIDCR NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - Netherlands
TA  - Antiviral Res
JT  - Antiviral research
JID - 8109699
RN  - 0 (Antiviral Agents)
RN  - 0 (Formazans)
RN  - 0 (Immediate-Early Proteins)
RN  - 0 (RNA, Viral)
RN  - 0 (Tetrazolium Salts)
RN  - 0 (herpes simplex virus, type 1 protein ICP4)
RN  - 23305-68-2 (MTT formazan)
RN  - 7BO8G1BYQU (Masoprocol)
SB  - IM
MH  - Animals
MH  - Antiviral Agents/*pharmacology
MH  - Chlorocebus aethiops
MH  - Drug Resistance, Microbial
MH  - Electrophoretic Mobility Shift Assay
MH  - Formazans/metabolism
MH  - Gene Expression Regulation, Viral/drug effects
MH  - Herpesvirus 1, Human/*drug effects/physiology
MH  - Immediate-Early Proteins/genetics/metabolism
MH  - Masoprocol/*analogs & derivatives/pharmacology
MH  - Mice
MH  - Promoter Regions, Genetic/genetics/physiology
MH  - RNA, Viral/chemistry/genetics
MH  - Surface Properties
MH  - Tetrazolium Salts/metabolism
MH  - Trigeminal Ganglion/virology
MH  - Vero Cells
MH  - Virus Activation/drug effects
MH  - Virus Replication/drug effects
EDAT- 2003/04/30 05:00
MHDA- 2003/08/13 05:00
CRDT- 2003/04/30 05:00
PHST- 2003/04/30 05:00 [pubmed]
PHST- 2003/08/13 05:00 [medline]
PHST- 2003/04/30 05:00 [entrez]
AID - S0166354202001651 [pii]
AID - 10.1016/s0166-3542(02)00165-1 [doi]
PST - ppublish
SO  - Antiviral Res. 2003 Mar;58(1):35-45. doi: 10.1016/s0166-3542(02)00165-1.