Ether Lipid Ester Derivatives of Cidofovir Inhibit Polyomavirus BK Replication In Vitro

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Ether lipid ester derivatives of cidofovir inhibit polyomavirus BK replication in vitro.

Polyomavirus BK is a significant pathogen in transplant recipients, but no effective antiviral therapy is available. We show that cidofovir can inhibit BK virus replication in vitro. Esterification of cidofovir with hexadecyloxypropyl, octadecyloxyethyl, and oleyloxyethyl groups results in up to a 3-log lowering of the 50% effective concentration and an increased selectivity index.

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Comparative activities of lipid esters of cidofovir and cyclic cidofovir against replication of herpesviruses in vitro.

Cidofovir (CDV) is an effective therapy for certain human cytomegalovirus (HCMV) infections in immunocompromised patients that are resistant to other antiviral drugs, but the compound is not active orally. To improve oral bioavailability, a series of lipid analogs of CDV and cyclic CDV (cCDV), including hexadecyloxypropyl-CDV and -cCDV and octadecyloxyethyl-CDV and -cCDV, were synthesized and f...

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Oral activity of ether lipid ester prodrugs of cidofovir against experimental human cytomegalovirus infection.

Infection with human cytomegalovirus (HCMV) can cause serious complications in bone-marrow and solid-organ transplant recipients, and current therapies are not optimal. We evaluated 2 orally active ether lipid ester analogues of cidofovir (CDV)--hexadecyloxypropyl-CDV (HDP-CDV) and octadecyloxyethyl-CVD (ODE-CDV)--in severe combined immunodeficient mice in which either human fetal retinal tissu...

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1-O-hexadecyloxypropyl cidofovir (CMX001) effectively inhibits polyomavirus BK replication in primary human renal tubular epithelial cells.

Antiviral drugs for treating polyomavirus BK (BKV) replication in polyomavirus-associated nephropathy or hemorrhagic cystitis are of considerable clinical interest. Unlike cidofovir, the lipid conjugate 1-O-hexadecyloxypropyl cidofovir (CMX001) is orally available and has not caused detectable nephrotoxicity in rodent models or human studies to date. Primary human renal proximal tubular epithel...

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miRNA regulation of BK polyomavirus replication during early infection.

Viral microRNAs (miRNAs) play an important role during infection by posttranscriptionally regulating both host and viral gene expression. However, the function of many viral miRNAs remains poorly understood. In this study, we investigated the role of the BK polyomavirus (BKPyV) miRNA in regulating virus replication. The function of the polyomavirus miRNA was investigated in archetype BKPyV, whi...

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ژورنال

عنوان ژورنال: Antimicrobial Agents and Chemotherapy

سال: 2006

ISSN: 0066-4804,1098-6596

DOI: 10.1128/aac.50.4.1564-1566.2006