(3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide) assays showed a lack of toxicity of ganciclovir (GCV), C.OXTs, and their derivatives, to TaY(OK) cells at 1 microM. Therefore we compared the antiviral potencies of these drugs at 1 microM by monitoring the viral loads produced during a 1-day period during the course of the drug treatment. Among the drugs tested, 3'-fluorocarbocyclic oxetanocin A (3'F-C.OXT-A) was the most effective for inhibiting the virus production, and at concentrations ranging from 0.5 microM to 10 microM, the inhibition of the viral production was dose-dependent. A comparison of the chemical structures of the derivatives with that of C.OXT-A, which is the parental molecule, suggested that the 3'-fluorine-modification might account for the higher anti-HHV-6 activity and lower cytotoxicity.
An infection of TaY cells, which originated from an adult T-cell leukemia, with an HHV-6B OK isolate resulted in a chronically infected culture, termed TaY(OK). Cell cloning analysis revealed that the TaY(OK) culture consisted of a mixture of cells permissive and refractory to the infection, and that the permissive cells were continuously produced from the refractory cell population. Since the chronically infected culture has been maintained for over 2 years without the addition of uninfected TaY cells, we used it for an evaluation of the antiviral potency of nucleoside analogs, especially carbocyclic oxetanocins (C.OXTs).
Wang
P
P
Department of Virology, Medical Research Institute, Tokyo Medical and Dental University, Japan.
Abe
K
K
Ojima
T
T
Ohyashiki
J H
JH
Satoh
H
H
Maruyama
T
T
Nagata
H
H
Tanaka
H
H
Yamamoto
K
K
D000225:Adenine / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D000998:Antiviral Agents / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015654:Herpesvirus 6, Human / Q000187:drug effects* / Q000502:physiology; D006801:Humans; D014407:Tumor Cells, Cultured; D014779:Virus Replication / Q000187:drug effects
D000998:Antiviral Agents; C051061:oxetanocin; D000225:Adenine