Inhibitory activity of 3′-fluoro-2′ deoxythymidine and related nucleoside analogues against adenoviruses in vitro1This paper is dedicated to Prof. Döhner on the occasion of his 65th birthday.1

Antiadenovirus Activities of Several Classes of Nucleoside and Nucleotide Analogues

“…The 2Ј,3Ј-dideoxynucleoside analogues zalcitabine and alovudine displayed potent and selective activity against adenovirus; their EC 50 s were in the same range as those obtained for cidofovir and (S)-HPMPA (0.7 to 3 M). The marked activity of zalcitabine and alovudine and inactivity of 5Ј-fluoro-2Ј,3Ј-dideoxyuridine, lamivudine, and zidovudine is in full agreement with other reports (19).…”

“…An intriguing finding is the inhibition of adenovirus DNA synthesis by 2Ј,3Ј-dideoxynucleoside analogues, as reported for zalcitabine (ddC) more than 20 years ago (27), and further documented by Mentel et al (19). At this time, alovudine (FddT) is in phase II trials for human immunodeficiency virus (HIV) therapy.…”

Anti-adenoviral effect of anti-HIV agents in vitro in serotypes inducing keratoconjunctivitis

“…None of the currently available anti-HIV agents has potent anti-AdV activity. We demonstrated marked antiAdV activity of zalcitabine, a nucleoside reverse transcriptase inhibitor (NRTI) [25], and it exhibits antiviral activity against AdV both in vitro and in vivo [22,23]. Higher drug concentrations in plasma may be difficult to achieve safely, given the dose-dependent mitochondrial toxicity of zalcitabine.…”

“…Case studies on the nucleoside analogue ribavirin have yielded conflicting results [1,8,19]. Recently, several investigators reported that cidofovir [6,9,10,31] and zalcitabine (ddC) [22,23] were effective in inhibiting AdV replication. Cidofovir was also found to be beneficial in several small-scale studies involving patients with lifethreatening AdV infections [1,12,20].…”

Adenovirus Infection in the Immunocompromised Host

“…Previously primarily used in the treatment of human immunodeficiency virus infection, zalcitabine (ddC/2',3'-dideoxycytidine) has been shown to have activity against adenovirus, both in vitro and in an animal model of adenovirus pneumonia (Mentel et al, 1997;Mentel and Wegner, 2000;Uchio et al, 2007). However, it has been pointed out that it is unlikely that adequate serum concentrations can be achieved without inducing significant mitochondrial toxicity .…”