PMID- 2984988
OWN - NLM
STAT- MEDLINE
DCOM- 19850514
LR  - 20190919
IS  - 0166-3542 (Print)
IS  - 0166-3542 (Linking)
VI  - 5
IP  - 1
DP  - 1985 Feb
TI  - Combination chemotherapy: interaction of 5-methoxymethyldeoxyuridine with 
      trifluorothymidine, phosphonoformate and acycloguanosine against herpes simplex 
      viruses.
PG  - 13-27
AB  - Methoxymethyldeoxyuridine (MMUdR) when used in combination with either 
      trifluorothymidine (F3TdR) or phosphonoformate (PFA) showed synergistic activity 
      against herpes simplex virus type 1 and type 2 (HSV-1 and HSV-2) in vitro, 
      whereas MMUdR and acycloguanosine (ACG) combination was antagonistic against 
      herpes viruses. HSV-1 mutants resistant to ACG, arabinofuranosyladenine (Ara-A), 
      MMUdR or PFA were isolated. Drug-resistant HSV-1 virus mutants were analyzed for 
      cross sensitivity to ACG, Ara-A, F3TdR, MMUdR, MMUdR-5'-monophosphate (MMUdR-MP) 
      and PFA. The Ara-A-resistant (Ara-AR) virus exhibited 3-fold resistance to 
      MMUdR-MP (ID50 = 105 microM). The ACG-resistant (ACGR) mutant was 160-fold less 
      sensitive to MMUdR (ID50 greater than 1138 microM). The MMUdR-resistant (MMUdRR) 
      mutant remained sensitive to all other antiviral drugs in vitro. Ara-A provided 
      protection against HSV-1 encephalitis in immunosuppressed mice inoculated with a 
      low dose (200 PFU/mouse) of MMUdRR virus or wild-type HSV-1. F3TdR decreased 
      incorporation of tritiated deoxyuridine [( 3H]UdR) in RK-13 cells by 50% at 0.068 
      microM. Under similar conditions, MMUdR (up to 600 microM) and PFA (up to 208 
      microM) were without effect on incorporation of [3H]UdR into DNA. In combination 
      chemotherapy experiments, MMUdR (up to 300 microM) used along with F3TdR (up to 
      1.08 microM) neither decreased nor enhanced cytotoxicity of F3TdR as measured by 
      incorporation of [3H]UdR into cellular DNA. Similarly, MMUdR (up to 300 microM) 
      in combination with PFA (up to 166 microM) was nontoxic to host cells.
FAU - Ayisi, N K
AU  - Ayisi NK
FAU - Gupta, S V
AU  - Gupta SV
FAU - Babiuk, L A
AU  - Babiuk LA
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Antiviral Res
JT  - Antiviral research
JID - 8109699
RN  - 0 (Antiviral Agents)
RN  - 0 (DNA, Viral)
RN  - 0 (Drug Combinations)
RN  - 0 (Organophosphorus Compounds)
RN  - 364P9RVW4X (Foscarnet)
RN  - 5116-22-3 (5-methoxymethyl-2'-deoxyuridine)
RN  - FA2DM6879K (Vidarabine)
RN  - N919E46723 (Phosphonoacetic Acid)
RN  - RMW9V5RW38 (Trifluridine)
RN  - VC2W18DGKR (Thymidine)
RN  - W78I7AY22C (Deoxyuridine)
RN  - X4HES1O11F (Acyclovir)
SB  - IM
MH  - Acyclovir/*administration & dosage
MH  - Animals
MH  - Antiviral Agents/*administration & dosage
MH  - DNA, Viral/biosynthesis
MH  - Deoxyuridine/*administration & dosage/analogs & derivatives
MH  - Drug Combinations
MH  - Drug Resistance, Microbial
MH  - Drug Synergism
MH  - Encephalitis/drug therapy
MH  - Foscarnet
MH  - Herpes Simplex/drug therapy
MH  - Male
MH  - Mice
MH  - Organophosphorus Compounds/*administration & dosage
MH  - Phosphonoacetic Acid/*administration & dosage/analogs & derivatives
MH  - Rabbits
MH  - Simplexvirus/*drug effects
MH  - Thymidine/*analogs & derivatives
MH  - Trifluridine/*administration & dosage
MH  - Vidarabine/therapeutic use
MH  - Virus Replication/drug effects
EDAT- 1985/02/01 00:00
MHDA- 1985/02/01 00:01
CRDT- 1985/02/01 00:00
PHST- 1985/02/01 00:00 [pubmed]
PHST- 1985/02/01 00:01 [medline]
PHST- 1985/02/01 00:00 [entrez]
AID - 0166-3542(85)90011-7 [pii]
AID - 10.1016/0166-3542(85)90011-7 [doi]
PST - ppublish
SO  - Antiviral Res. 1985 Feb;5(1):13-27. doi: 10.1016/0166-3542(85)90011-7.