Targeting Parvovirus B19: antiviral strategies reviewed

Introduction Parvovirus B19 (B19V), a human pathogenic ssDNA virus in the Parvoviridae family, is responsible for a wide range of clinical manifestations, including severe clinical manifestations in patients with underlying haematological disorders or with immune system deficits. Currently, there are no recognized antiviral drugs for B19V treatment therefore ongoing research is directed towards the identification of compounds inhibiting B19V replication. In our activity, different approaches to antiviral discovery have been followed until now: drug repositioning strategy, screening of known antiviral compounds for a possible activity against B19 and a serendipity approach in screening small chemical libraries of compounds with possible antiviral activity. Methods Two cellular systems can be used to support viral replication in vitro and study the antiviral activity of tested compounds: the cell line UT7/EpoS1, although permissiveness is restricted to only a subset of cells, and primary erythroid progenitor cells (EPCs) that more closely resemble the natural target cells within the bone marrow environment. The antiviral effects of tested compounds can be evaluated by qPCR-based assays, to measure the variation in the abundance of viral DNA or mRNAs following a course of infection. In situ hybridization assays for viral nucleic acids or immunological detection of viral proteins, can be used to measure variations in the frequency of productively infected cells. Results The drug repositioning approach identified Hydroxyurea, an antiproliferative drug for sickle-cell disease, as effective against B19V, while Methotrexate, a folic acid analogue and antagonist used as an anti-inflammatory drug, showed no antiviral activity. Nucleotide analogues and its lipid conjugate, Cidofovir and Brincidofovir, demonstrated the most effective antiviral activity against B19V. Platinum-conjugated nucleotides with anticancer activity were investigated but are limited by cytotoxicity to EPCs. Foscarnet's clinical use has been reported, but only a low in vitro efficacy has been confirmed. The serendipity approach, based on screening small chemical libraries of compounds with potential antiviral activity, led to the discovery of promising coumarin derivatives. Lastly, Ivermectins/Avermectins were shown to block the nuclear import of viral NS1 protein, inhibiting replication. Discussion and conclusions The results obtained suggest that various drugs, known for their use also in other therapeutic areas, could potentially be repurposed against B19V. However, further studies are required to confirm the potential of these drugs and explore their clinical application.