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The results show that NAPs inhibit HDV infection at concentrations less than 4 \u03bcM in cultures of differentiated human hepatoma cells. NAPs were shown to be active at viral entry but inactive postentry on HDV RNA replication. Inhibition was independent of the NAP nucleotide sequence but dependent on both size and amphipathicity of the polymer. NAP antiviral activity was effective against HDV virions bearing the main hepatitis B virus (HBV) immune escape substitutions (D144A and G145R) and was pangenomic with regard to HBV envelope proteins. Furthermore, similar to immobilized heparin, immobilized NAPs could bind HDV particles, suggesting that entry inhibition was due, at least in part, to preventing attachment of the virus to cell surface glycosaminoglycans. The results document NAPs as a novel class of antiviral compounds that can prevent HDV propagation.<\/jats:p><jats:p><jats:bold>IMPORTANCE<\/jats:bold>HDV infection causes the most severe form of viral hepatitis in humans and one of the most difficult to cure. Currently, treatments are limited to long-term administration of interferon at high doses, which provide only partial efficacy. There is thus an urgent need for innovative approaches to identify new antiviral against HDV. The significance of our study is in demonstrating that nucleic acid polymers (NAPs) are active against HDV by targeting the envelope of HDV virions. In an<jats:italic>in vitro<\/jats:italic>infection assay, NAP activity was recorded at concentrations less than 4 \u03bcM in the absence of cell toxicity. Furthermore, the fact that NAPs could block HDV at viral entry suggests their potential to control the spread of HDV in a chronically HBV-infected liver. In addition, NAP anti-HDV activity was pangenomic with regard to HBV envelope proteins and not circumvented by HBsAg substitutions associated with HBV immune escape.<\/jats:p>","DOI":"10.1128\/jvi.01416-17","type":"journal-article","created":{"date-parts":[[2017,12,6]],"date-time":"2017-12-06T16:20:32Z","timestamp":1512577232000},"update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":41,"title":["Nucleic Acid Polymers Are Active against Hepatitis Delta Virus Infection<i>In Vitro<\/i>"],"prefix":"10.1128","volume":"92","author":[{"given":"Frauke","family":"Beilstein","sequence":"first","affiliation":[{"name":"Institut National de la Transfusion Sanguine (INTS), CNRS-INSERM U1134, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthieu","family":"Blanchet","sequence":"additional","affiliation":[{"name":"Replicor Inc., Montreal, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Vaillant","sequence":"additional","affiliation":[{"name":"Replicor Inc., Montreal, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Camille","family":"Sureau","sequence":"additional","affiliation":[{"name":"Institut National de la Transfusion Sanguine (INTS), CNRS-INSERM U1134, Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/s0140-6736(15)61412-x"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.jhep.2016.02.013"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1101\/cshperspect.a021576"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1002\/hep.27102"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa0912696"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9673(01)93098-5"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.virol.2007.10.016"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.50.4.1393-1401.2006"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1128\/AAC.00279-08"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1186\/1743-422X-6-214"},{"key":"e_1_3_2_12_2","doi-asserted-by":"crossref","first-page":"1147","DOI":"10.1177\/135965350701200810","article-title":"Amphipathic DNA polymers are candidate vaginal microbicides and block herpes simplex virus binding, entry and viral gene expression","volume":"12","author":"Guzman EM","year":"2007","unstructured":"Guzman EM, Cheshenko N, Shende V, Keller MJ, Goyette N, Juteau JM, Boivin G, Vaillant A, Herold BC. 2007. 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