ACTIVITIES OF VARIOUS COMPOUNDS AGAINST MURINE AND PRIMATE POLYOMAVIRUSES

Polyomavirus infections in humans are due to BK virus (BKV) and JC vir us (JCV), Diseases associated with human polyomaviruses occur mostly i n immunocompromised adults, e,g,, progressive multifocal leukoencephal opathy (PML), caused by JCV, in AIDS patients and hemorrhagic cystitis and uretral stenosis, caused by BKV, in transplant recipients, No the rapy is available for these diseases, which necessitates the developme nt of chemical entities that are active against polyomaviruses, Severa l antiviral compounds were evaluated to determine their effects on the in vitro replication of mouse polyomavirus and the primate viruses si mian virus 40 (SV40), SV40 PML-1, and SV40 PML-2, The activity of the different compounds was assessed by a cytopathic effect reduction assa y and confirmed in a virus yield assay, Cidofovir [HPMPC; )-1-(3-hydro xy-2-phosphonylmethoxypropyl)cytosine] and its cyclic counterpart emer ged as the most selective antipolyomavirus agents, The 50% inhibitory concentrations for HPMPC were in the range of 4 to 7 mu g/ml, and its selectivity index varied from 11 to 20 for mouse polyomavirus and from 23 to 33 for SV40 strains in conflueut cell monolayers, Cell cytotoxi city was up to 15-fold greater in growing cells, Other acyclic nucleos ide phosphonates (i,e,, HPMPA; S)-9-(3-hydroxy-2-phosphonylmethoxyprop yl)adenine] and PMEG [9-(2-phosphonylmethoxyethyl)-guanine]) also show ed some activity but had low selectivity, None of the other drugs test ed against these animal viruses (i,e,, acyclovir, ganciclovir, brivudi ne, ribavirin, foscarnet, and cytarabine) showed significant activity, Thus, HPMPC deserves further evaluation as a candidate drug for polyo mavirus infections in the immuno-compromised host.