Antiviral Res 2019[Feb]; 162 (ä): 22-29 PMID30529090show ga
Parvovirus B19 (B19V), a single-stranded DNA virus in the family Parvoviridae, is a human pathogenic virus responsible for a wide range of clinical manifestations. Currently there is no approved antiviral therapy for parvovirus infection. The acyclic nucleoside phosphonate cidofovir (CDV) has been demonstrated to inhibit replication of B19V in vitro. The aim of the present study was to evaluate whether brincidofovir (BCV), a novel lipid conjugate of CDV, could also inhibit B19V replication. Experiments were carried out in erythroid progenitor cells (EPCs) and UT7/EpoS1 cells, infected with B19V and cultured in the presence of different concentrations of BCV and CDV for comparison. The dynamics of viral replication was evaluated by a qPCR-based assay and the extent of inhibition of viral replication exerted by the compounds determined, along with the effect of the compounds on cell viability and cell proliferation rates. Results confirmed that BCV showed significantly higher antiviral activity against B19V compared to CDV in both cell-based systems. For BCV, the calculated EC(50) values were in the range 6.6-14.3?muM in EPCs and 0.22-0.63?muM in UT7/EpoS1 cells. In comparison, the EC(50) values for CDV were >300?muM in EPCs and 16.1?muM in UT7/EpoS1 cells. Concurrently, the effects on cell viability were observed at a much higher concentration of BCV, with calculated CC(50) values in the range 93.4-102.9?muM in EPCs and 59.9-66.8?muM in UT7/Epos1. The antiviral activity was observed specifically with the metabolically active stereoisomer of BCV suggesting that CDV-diphosphate, the metabolite of both BCV and CDV, was the active antiviral. Our results support a selective role for BCV in the inhibition of B19 viral replication.
Antiviral+Res 2019 ; 162 (ä): 22-29
