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dependent on the metabolism of the infected cell: therefore, it has been used to
study cellular and molecular functions. Classical works based on the study of the
viral proliferation helped to elucidate the mechanisms of the regulation of DNA
replication, RNA transcription, and translation as well as tumor transformation.
Analogously to other polyomaviruses, with which it shares a high sequence homo-
logy, Py can very effi ciently transform non permissive cells in culture and is able
to cause tumors if injected in immuno-suppressed or singeneic animals (see: [1]
for a compendium on polyomaviruses and [2-7] for more recent reviews on this
subject).
In last decade we investigated the role of both natural and synthetic substances on
Py DNA replication and RNA transcription [8-10]. Also, the cellular and metabolic re-
sponse after exposure to these substances was studied [11-15]. We particularly focused
our attention on a natural complex mixture, known as MEX, obtained by methanolic
extraction of whole neem oil [13]. This oil is prepared from the seeds of Azadirachta
indica and has been extensively used in Ayurveda, Unani, and Homoeopathic medi-
cine possibly for centuries [16, 17]. In our laboratory MEX showed a signifi cant and
differential cytotoxic action, with the cancer cells being more sensitive than the nor-
mal ones [18]. The main target of MEX is the plasma membrane which, after treatment
with this extract, becomes more fl uid without a substantial loss of its structural prop-
erties [19]. In addition, preliminary experiments performed in our laboratory suggest
that MEX has also an antiviral activity (Berardi et al., in preparation); in any case a
similar activity of neem leaf extracts was reported in a model of Dengue virus [20].
In this work we assayed the action of RV, a natural compound raising an increasing
interest on the proliferation of cultured cells that is : the murine fi broblast line 3T6 as
well as in the tumor line HL60. In addition, we also investigated the action of this drug
on the proliferation of the Py in the infected cell population.
The RV is a non-fl avonoid polyphenol compound present in many plants and
fruits, at especially high concentrations in the grape berries of Vitis vinifera [21]. This
compound has a high bioactivity and its cytoprotective action has been demonstrated.
As a matter of fact, possibly due to its polyphenol characteristics, RV was also shown
to have antiviral action versus infl uenza A [22] and Varicella zoster virus in cultured
cells [23]. Analogous properties of RV against Herpes virus simplex I were shown
in animal models [24]. In this latter case, suppression of transcription factor NF-κ-B
seems to be involved in its antiviral property [25].
The results presented here show that RV exhibits a cytotoxic activity and has an
antiviral property since it effi ciently inhibits the synthesis of Py DNA. The inhibition
is observed at non cytotoxic concentrations of RV as shown by vital cell count and
quantitative evaluation of the viral DNA synthesis after exposure to the drug. In ad-
dition, our results evidence a clear dose dependent antiviral effect of RV. Since this
action appears after the phase of virion penetration, data suggest that RV exerts its an-
tiviral properties during the synthesis of the viral DNA progeny. However, because of
its cytotoxic properties, it may be envisaged an application of RV to control negatively
the cell growth in proliferative diseases.
 
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