Hydroxyurea inhibits parvovirus B19 replication in erythroid progenitor cells

Bonvicini, Francesca; Bua, Gloria; Conti, Ilaria; Manaresi, Elisabetta; Gallinella, Giorgio

doi:10.1016/j.bcp.2017.03.022

Cited by 25 publications

(13 citation statements)

References 38 publications

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“…Although the mode of action of hydroxyurea for HCV, HBV, HSV, and B19V is unknown, viral replications were inhibited by hydroxyurea in in vitro studies. 70 , 74 – 76 Small-scaled clinical trials showed significant reduction of HCV RNA levels and HBV viral loads in chronic HCV and HBV carriers, respectively. 71 , 72 However, there is a case report of an elderly patient with essential thrombocythemia experiencing reactivation of HBV during treatment with hydroxyurea.…”

Section: Part Ii: Dmards With Antiviral Potential Other Than Sars-covmentioning

confidence: 99%

Oral disease-modifying antirheumatic drugs and immunosuppressants with antiviral potential, including SARS-CoV-2 infection: a review

Tsai

2020

Therapeutic Advances in Musculoskeletal

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There have been several episodes of viral infection evolving into epidemics in recent decades, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the latest example. Its high infectivity and moderate mortality have resulted in an urgent need to find an effective treatment modality. Although the category of immunosuppressive drugs usually poses a risk of infection due to interference of the immune system, some of them have been found to exert antiviral properties and are already used in daily practice. Recently, hydroxychloroquine and baricitinib have been proposed as potential drugs for SARS-CoV-2. In fact, there are other immunosuppressants known with antiviral activities, including cyclosporine A, hydroxyurea, minocycline, mycophenolic acid, mycophenolate mofetil, leflunomide, tofacitinib, and thalidomide. The inherent antiviral activity could be a treatment choice for patients with coexisting rheumatological disorders and infections. Clinical evidence, their possible mode of actions and spectrum of antiviral activities are included in this review article. Lay summary Immunosuppressants often raise the concern of infection risks, especially for patients with underlying immune disorders. However, some disease-modifying antirheumatic drugs (DMARDs) with inherent antiviral activity would be a reasonable choice in the situation of concomitant viral infections and flare up of autoimmune diseases. This review covers DMARDs of treatment potential for SARS-CoV-2 in part I, and antiviral mechanisms plus trial evidence for viruses other than SARS-CoV-2 in part II.

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Section: Part Ii: Dmards With Antiviral Potential Other Than Sars-covmentioning

confidence: 99%

Oral disease-modifying antirheumatic drugs and immunosuppressants with antiviral potential, including SARS-CoV-2 infection: a review

Tsai

2020

Therapeutic Advances in Musculoskeletal

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“…Alternative approaches to antiviral discovery have been followed until now: a strategy based on drug repositioning; a strategy based on investigation of known antiviral compounds for a possible activity against B19V; a serendipity approach in screening small chemical libraries of compounds with possible antiviral activity; and a search for direct antiviral compounds by targeted biochemical screening. The first approach yielded antiviral activity provided by the cell-proliferation inhibitor hydroxyurea (HU) [82], also used as a disease-modifying drug in the treatment of sickle cell disease. The second approach first yielded the acyclic nucleoside phosphonate cidofovir (CDV) [83,84], though with suboptimal activity, and then its lipid conjugate brincidofovir (BCV) [85], with substantially enhanced activity.…”

Section: The Quest For Antiviral Agentsmentioning

confidence: 99%

“…Experimentally, HU demonstrated a measurable inhibitory effect on B19V replication in both EPCs and UT7/EpoS1 cells [82]. Complete inhibition of viral replication was obtained at >1 mM, and observed EC 50 values were 96.2 µM and 147.1 µM in UT7/EpoS1 and EPCs, respectively.…”

Section: The Quest For Antiviral Agentsmentioning

confidence: 99%

Advances in the Development of Antiviral Strategies against Parvovirus B19

Manaresi

Gallinella

2019

Viruses

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Parvovirus B19 (B19V) is a human pathogenic virus, responsible for an ample range of clinical manifestations. Infections are usually mild, self-limiting, and controlled by the development of a specific immune response, but in many cases clinical situations can be more complex and require therapy. Presently available treatments are only supportive, symptomatic, or unspecific, such as administration of intravenous immunoglobulins, and often of limited efficacy. The development of antiviral strategies against B19V should be considered of highest relevance for increasing the available options for more specific and effective therapeutic treatments. This field of research has been explored in recent years, registering some achievements as well as interesting future perspectives. In addition to immunoglobulins, some compounds have been shown to possess inhibitory activity against B19V. Hydroxyurea is an antiproliferative drug used in the treatment of sickle-cell disease that also possesses inhibitory activity against B19V. The nucleotide analogues Cidofovir and its lipid conjugate Brincidofovir are broad-range antivirals mostly active against dsDNA viruses, which showed an antiviral activity also against B19V. Newly synthesized coumarin derivatives offer possibilities for the development of molecules with antiviral activity. Identification of some flavonoid molecules, with direct inhibitory activity against the viral non-structural (NS) protein, indicates a possible line of development for direct antiviral agents. Continuing research in the field, leading to better knowledge of the viral lifecycle and a precise understanding of virus–cell interactions, will offer novel opportunities for developing more efficient, targeted antiviral agents, which can be translated into available therapeutic options.

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“…The development of antiviral strategies directed against B19V as compared to other viruses is still lagging, although recent work has identified a few compounds that show a selective inhibition of B19V replication in vitro [16]. Such compounds include hydroxyurea (HU), a ribonucleotide reductase inhibitor, also used for the treatment of sickle-cell disease and known to have "virostatic" properties [17]; the nucleotide analogues cidofovir (CDV) and its lipid derivative brincidofovir (BCV), broad-spectrum anti-viral agents mostly active against dsDNA viruses [18][19][20]; and a few coumarin derivatives [21]. Some flavonoid compounds can inhibit the endonuclease activity of viral NS protein, a function critical to the replicative process of B19V [22].…”

Section: Introductionmentioning

confidence: 99%

No G-Quadruplex Structures in the DNA of Parvovirus B19: Experimental Evidence versus Bioinformatic Predictions

Bua

Tedesco

Conti

et al. 2020

Viruses

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Parvovirus B19 (B19V), an ssDNA virus in the family Parvoviridae, is a human pathogenic virus, responsible for a wide range of clinical manifestations, still in need of effective and specific antivirals. DNA structures, including G-quadruplex (G4), have been recognised as relevant functional features in viral genomes, and small-molecule ligands binding to these structures are promising antiviral compounds. Bioinformatic tools predict the presence of potential G4 forming sequences (PQSs) in the genome of B19V, raising interest as targets for antiviral strategies. Predictions locate PQSs in the genomic terminal regions, in proximity to replicative origins. The actual propensity of these PQSs to form G4 structures was investigated by circular dichroism spectroscopic analysis on synthetic oligonucleotides of corresponding sequences. No signature of G4 structures was detected, and the interaction with the G4 ligand BRACO-19 (N,N′-(9-{[4-(dimethylamino)phenyl]amino}acridine-3,6-diyl)bis(3-pyrrolidin-1-ylpropanamide) did not appear consistent with the stabilisation of G4 structures. Any potential role of PQSs in the viral lifecycle was then assessed in an in vitro infection model system, by evaluating any variation in replication or expression of B19V in the presence of the G4 ligands BRACO-19 and pyridostatin. Neither showed a significant inhibitory activity on B19V replication or expression. Experimental challenge did not support bioinformatic predictions. The terminal regions of B19V are characterised by relevant sequence and symmetry constraints, which are functional to viral replication. Our experiments suggest that these impose a stringent requirement prevailing over the propensity of forming actual G4 structures.

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Hydroxyurea inhibits parvovirus B19 replication in erythroid progenitor cells

Cited by 25 publications

References 38 publications

Oral disease-modifying antirheumatic drugs and immunosuppressants with antiviral potential, including SARS-CoV-2 infection: a review

Oral disease-modifying antirheumatic drugs and immunosuppressants with antiviral potential, including SARS-CoV-2 infection: a review

Advances in the Development of Antiviral Strategies against Parvovirus B19

No G-Quadruplex Structures in the DNA of Parvovirus B19: Experimental Evidence versus Bioinformatic Predictions

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