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Article

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

Department of Pharmacy and Biotechnology, University of Bologna, 40126 Bologna, Italy
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Current address: Institute for Organic Synthesis and Photoreactivity (ISOF), National Research Council (CNR), 40129 Bologna, Italy.
§
Current address: Department of Morphology, Surgery and Experimental Medicine, University of Ferrara, 44121 Ferrara, Italy.
Current address: Unit of Microbiology, Alma Mater Studiorum-University of Bologna, S. Orsola-Malpighi Hospital, Via Massarenti 9, 40138 Bologna, Italy.
Received: 27 July 2020 / Revised: 20 August 2020 / Accepted: 21 August 2020 / Published: 25 August 2020
(This article belongs to the Special Issue Advances in Parvovirus Research 2020)
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. View Full-Text
Keywords: parvovirus B19; G-quadruplex; bioinformatics; antivirals; BRACO-19; pyridostatin parvovirus B19; G-quadruplex; bioinformatics; antivirals; BRACO-19; pyridostatin
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MDPI and ACS Style

Bua, G.; Tedesco, D.; Conti, I.; Reggiani, A.; Bartolini, M.; Gallinella, G. No G-Quadruplex Structures in the DNA of Parvovirus B19: Experimental Evidence versus Bioinformatic Predictions. Viruses 2020, 12, 935. https://0-doi-org.brum.beds.ac.uk/10.3390/v12090935

AMA Style

Bua G, Tedesco D, Conti I, Reggiani A, Bartolini M, Gallinella G. No G-Quadruplex Structures in the DNA of Parvovirus B19: Experimental Evidence versus Bioinformatic Predictions. Viruses. 2020; 12(9):935. https://0-doi-org.brum.beds.ac.uk/10.3390/v12090935

Chicago/Turabian Style

Bua, Gloria, Daniele Tedesco, Ilaria Conti, Alessandro Reggiani, Manuela Bartolini, and Giorgio Gallinella. 2020. "No G-Quadruplex Structures in the DNA of Parvovirus B19: Experimental Evidence versus Bioinformatic Predictions" Viruses 12, no. 9: 935. https://0-doi-org.brum.beds.ac.uk/10.3390/v12090935

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