Ether lipid ester derivatives of cidofovir inhibit polyomavirus BK replication in vitro.
نویسندگان
چکیده
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.
منابع مشابه
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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BACKGROUND Polyomavirus-associated nephropathy (PVAN) is a serious complication and cause of graft loss in kidney transplant recipients. In the absence of specific antiviral drugs, early detection of the disease and reduction of immunosuppressive regimen is the cornerstone of therapy. Cidofovir, a nucleoside analogue, has been found to inhibit BK virus (BKV) replication in vitro and has been pr...
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BK virus (BKV), a virus belonging to the polyomavirus family, is a circular double-stranded DNA virus that causes nephropathies in immunocompromised patients after kidney or bone marrow transplantation. The occurrence of polyomavirus-associated nephropathy in kidney transplant patients may trigger graft loss, and guidelines for the management of BKV infection have not yet been clearly establish...
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متن کاملAnti-BK virus activity of nucleoside analogs.
Polyomavirus BK is an important pathogen in transplant recipients with no effective therapy. This study demonstrates that alkoxyalkyl esters of (S)-9-(3-hydroxy-2-phosphonylmethoxypropyl)adenine and fatty acid derivatives of 9-[2-(phosphonomethyoxy)ethyl]adenine (P393 and P405) are potent and selective inhibitors of BK virus replication in vitro, with a 50% effective concentration in the microm...
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عنوان ژورنال:
- Antimicrobial agents and chemotherapy
دوره 50 4 شماره
صفحات -
تاریخ انتشار 2006