Activities of Different Classes of Acyclic Nucleoside Phosphonates against BK Virus in Primary Human Renal Cells

Abstract

BK virus (BKV),

Insights into the mechanism of action of cidofovir and other acyclic nucleoside phosphonates against polyoma- and papillomaviruses and non-viral induced neoplasia

“…SV40) (Andrei et al, 1997;Lebeau et al, 2007) as well as against human BKPyV and JCPyV (Topalis et al, 2011;Farasati et al, 2005;Gosert et al, 2011;Rinaldo et al, 2010) replication in vitro. Despite CDV shows modest in vitro activity against BKPyV, CDV is the drug most frequently used clinically to block BKPyV replication.…”

Evaluation and Management of BK Virus-Associated Nephropathy Following Allogeneic Hematopoietic Cell Transplantation

“…Cidofovir ([S]-1-[3-hydroxy-2-(phosphonomethoxy) propyl] cytosine [HPMPC]) is an acyclic phosphonate analogue of dCMP, which has shown antiviral activity against several DNA viruses, including BK virus, although its mechanism of action is still under investigation. New classes of nucleoside phosphonate derivatives are under investigation [31]. Leflunomide is an immunomodulatory agent that inhibits pyrimidine synthesis and results in antiproliferative and anti inflammatory effects.…”

“…In a comparison study of cidofovir against leflunomide for the treatment of BK nephropathy in solid organ transplants, both drugs had similar rates of clearing BK viremia, but there was less graft loss seen with the use of leflunomide [35]. Of interest, in 1 study evaluating the inhibitory effects of cidofivir against leflunomide against BK virus replication in vitro, cidofivir was noted to be superior [31]. …”

Extent of intramolecular π stacks in aqueous solution in mixed-ligand copper(II) complexes formed by heteroaromatic amines and the anticancer and antivirally active 9-[2-(phosphonomethoxy)ethyl]guanine (PMEG). A comparison with related acyclic nucleotide analogues

“…HPMPC, also known as Cidofovir, was approved in 1996 for the treatment of cytomegalovirus retinitis in patients with AIDS [10]. However, new antiviral activities of HPMPC and of related analogues are still being discovered [6,7] and various prodrug forms are studied [11][12][13] which give rise to higher activities due to an increased bioavailability, e.g., against HIV-1 [12], herpesviruses [11] or orthopoxviruses [11].…”

“…These reveal that in the monoprotonated ternary Cu(Arm)(H;PE) + complexes, the proton and Cu(Arm) 2+ Since the discovery that the human immunodeficiency virus (HIV) is the causative agent of the acquired immunodeficiency syndrome (AIDS) [3], there have been numerous attempts to find remedies against this retrovirus [4,5]; in fact, against viral diseases in general [4][5][6][7]. One of the popular and relatively successful classes of compounds are so-called acyclic nucleoside phosphonates (ANPs) [8].…”