Clinical uses of cidofovir

Safrin, Sharon; Cherrington, Julie M.; Jaffe, Howard S.

doi:10.1002/(sici)1099-1654(199709)7:3<145::aid-rmv196>3.0.co;2-0

Cited by 162 publications

(87 citation statements)

References 57 publications

(69 reference statements)

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“…23,24 Cidofovir also has a broad spectrum of activity against other viruses such as human herpes virus, adenovirus, polyomavirus, and human poxviruses. 25 Cidofovir was effective against all six species of human adenovirus at 17-81 mM, 21 a dose very similar to 10 mM used in this study. We opted for the lowest drug dose that blocked the virus without damaging cells.…”

Section: Effect Of Cidofovir On Gene Expressionmentioning

confidence: 68%

Viral mRNA expression but not DNA replication is required for lipogenic effect of human adenovirus Ad-36 in preadipocytes

Rathod

Vangipuram²,

Krishnan

et al. 2006

Int J Obes

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Objective: Human adenovirus Ad-36 causes adiposity in animal models and shows association with human obesity. Ad-36 enhances differentiation of 3T3-L1 and human preadipocytes, without cell lysis, a characteristic that may contribute to its adipogenic effect observed in vivo. Ad-2, another human adenovirus is nonadipogenic in animals and in 3T3-L1 cells and shows no correlation with human obesity. The objective of this study was to determine the adipogenic roles of viral mRNA and DNA, which may explain the differential effects of Ad-36 and Ad-2 on preadipocyte differentiation. Methods: This study determined the duration of selected Ad-36 gene expression in 3T3-L1 cells, and the effect on preadipocytes differentiation, when Ad-36 gene expression was attenuated by Cidofovir, an antiadenoviral agent. Results:The results showed that Ad-36, but not Ad-2, expresses viral mRNA. Ad-36 gene expression peaked at 2-4 days postinoculation and very low levels persisted after day 7. Despite the viral mRNA expression, Ad-36 infection of 3T3-L1 cells was abortive as indicated by a progressive decrease in viral DNA quantity. Attenuation of Ad-36 mRNA expression by Cidofovir reduced the adipogenic effect of the virus. Conclusion: In conclusion, viral mRNA expression, although transient, is a prerequisite for enhancing differentiation of preadipocytes by Ad-36. Viral DNA replication was not required for the effect. This is the first evidence for the role of gene expression of an adipogenic human virus in enhancing preadipocytes differentiation. This study provides the basis for further understanding novel regulatory modulators of preadipocytes differentiation.

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Section: Effect Of Cidofovir On Gene Expressionmentioning

confidence: 68%

Viral mRNA expression but not DNA replication is required for lipogenic effect of human adenovirus Ad-36 in preadipocytes

Rathod

Vangipuram²,

Krishnan

et al. 2006

Int J Obes

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“…Hyperhydration together with coadministration of the drug probenecid has been shown to have a nephroprotective effect. 47,48 Probenecid is an organic acid that competes for the kidney's organic anion transporter and thereby protects tubule cells and increases cidofovir plasma level.…”

Section: Antiviral Drugsmentioning

confidence: 99%

How I treat adenovirus in hematopoietic stem cell transplant recipients

Lindemans

Leen

Boelens

2010

Blood

212

215

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“…In a comparative study of cidofovir activity against different poxviruses (92), the following IC 50 s were noted (in Vero cells): VV, 18 g/ml; cowpox virus, 16 g/ml; camelpox virus, 5 g/ml; monkeypox virus, 19 g/ml; variola virus, 1.5 g/ml (data from J. Huggins, mentioned in reference 92). This study indicated that the smallpox virus variola virus was even more sensitive to the inhibitory effects of cidofovir than VV was.…”

Section: (S)-hpmpcp (S)-hpmpcpp and (S)-hpmpcp-choline]; In Particumentioning

confidence: 99%

Vaccinia Virus Inhibitors as a Paradigm for the Chemotherapy of Poxvirus Infections

2001

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Poxviruses continue to pose a major threat to human health. Monkeypox is endemic in central Africa, and the discontinuation of the vaccination (with vaccinia virus) has rendered most humans vulnerable to variola virus, the etiologic agent of smallpox, should this virus be used in biological warfare or terrorism. However, a large variety of compounds have been described that are potent inhibitors of vaccinia virus replication and could be expected to be active against other poxviruses as well. These compounds could be grouped in different classes: (i) IMP dehydrogenase inhibitors (e.g., EICAR); (ii) SAH hydrolase inhibitors (e.g., 5′-noraristeromycin, 3-deazaneplanocin A, and various neplanocin A derivatives); (iii) OMP decarboxylase inhibitors (e.g., pyrazofurin) and CTP synthetase inhibitors (e.g., cyclopentenyl cytosine); (iv) thymidylate synthase inhibitors (e.g., 5-substituted 2′-deoxyuridines); (v) nucleoside analogues that are targeted at viral DNA synthesis (e.g., Ara-A); (vi) acyclic nucleoside phosphonates [e.g., (S)-HPMPA and (S)-HPMPC (cidofovir)]; and (vii) polyanionic substances (e.g., polyacrylic acid). All these compounds could be considered potential candidate drugs for the therapy and prophylaxis of poxvirus infections at large. Some of these compounds, in particular polyacrylic acid and cidofovir, were found to generate, on single-dose administration, a long-lasting protective efficacy against vaccinia virus infection in vivo. Cidofovir, which has been approved for the treatment of cytomegalovirus retinitis in immunocompromised patients, was also found to protect mice, again when given as a single dose, against a lethal aerosolized or intranasal cowpox virus challenge. In a biological warfare scenario, it would be advantageous to be able to use a single treatment for an individual exposed to an aerosolized poxvirus. Cidofovir thus holds great promise for treating human smallpox, monkeypox, and other poxvirus infections. Anecdotal experience points to the efficacy of cidofovir in the treatment of the poxvirus infections molluscum contagiosum and orf (ecthyma contagiosum) in immunosuppressed patients

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Clinical uses of cidofovir

Cited by 162 publications

References 57 publications

Viral mRNA expression but not DNA replication is required for lipogenic effect of human adenovirus Ad-36 in preadipocytes

Viral mRNA expression but not DNA replication is required for lipogenic effect of human adenovirus Ad-36 in preadipocytes

How I treat adenovirus in hematopoietic stem cell transplant recipients

Vaccinia Virus Inhibitors as a Paradigm for the Chemotherapy of Poxvirus Infections

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