{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,9]],"date-time":"2026-09-09T04:59:41Z","timestamp":1788929981046,"version":"build-2803163510"},"reference-count":99,"publisher":"MDPI AG","issue":"11","license":[{"start":{"date-parts":[[2020,11,7]],"date-time":"2020-11-07T00:00:00Z","timestamp":1604707200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Science Center","award":["UMO-2019\/35\/D\/NZ6\/01479"],"award-info":[{"award-number":["UMO-2019\/35\/D\/NZ6\/01479"]}]},{"name":"National Science Center","award":["UMO-2020\/01\/0\/NZ6\/00137"],"award-info":[{"award-number":["UMO-2020\/01\/0\/NZ6\/00137"]}]},{"name":"National Science Center","award":["UMO-2019\/33\/B\/ST4\/01422"],"award-info":[{"award-number":["UMO-2019\/33\/B\/ST4\/01422"]}]},{"name":"National Science Center","award":["UMO-2017\/25\/B\/NZ1\/02269"],"award-info":[{"award-number":["UMO-2017\/25\/B\/NZ1\/02269"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pathogens"],"abstract":"<jats:p>Influenza is an important research subject around the world because of its threat to humanity. Influenza A virus (IAV) causes seasonal epidemics and sporadic, but dangerous pandemics. A rapid antigen changes and recombination of the viral RNA genome contribute to the reduced effectiveness of vaccination and anti-influenza drugs. Hence, there is a necessity to develop new antiviral drugs and strategies to limit the influenza spread. IAV is a single-stranded negative sense RNA virus with a genome (viral RNA\u2014vRNA) consisting of eight segments. Segments within influenza virion are assembled into viral ribonucleoprotein (vRNP) complexes that are independent transcription-replication units. Each step in the influenza life cycle is regulated by the RNA and is dependent on its interplay and dynamics. Therefore, viral RNA can be a proper target to design novel therapeutics. Here, we briefly described examples of anti-influenza strategies based on the antisense oligonucleotide (ASO), small interfering RNA (siRNA), microRNA (miRNA) and catalytic nucleic acids. In particular we focused on the vRNA structure-function relationship as well as presented the advantages of using secondary structure information in predicting therapeutic targets and the potential future of this field.<\/jats:p>","DOI":"10.3390\/pathogens9110925","type":"journal-article","created":{"date-parts":[[2020,11,8]],"date-time":"2020-11-08T19:03:37Z","timestamp":1604862217000},"page":"925","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":31,"title":["RNA Secondary Structure as a First Step for Rational Design of the Oligonucleotides towards Inhibition of Influenza A Virus Replication"],"prefix":"10.3390","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5772-0808","authenticated-orcid":false,"given":"Marta","family":"Szabat","sequence":"first","affiliation":[{"name":"Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12\/14, 61-704 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8276-3746","authenticated-orcid":false,"given":"Dagny","family":"Lorent","sequence":"additional","affiliation":[{"name":"Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12\/14, 61-704 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8124-1003","authenticated-orcid":false,"given":"Tomasz","family":"Czapik","sequence":"additional","affiliation":[{"name":"Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12\/14, 61-704 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maria","family":"Tomaszewska","sequence":"additional","affiliation":[{"name":"Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12\/14, 61-704 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5563-003X","authenticated-orcid":false,"given":"Elzbieta","family":"Kierzek","sequence":"additional","affiliation":[{"name":"Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12\/14, 61-704 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryszard","family":"Kierzek","sequence":"additional","affiliation":[{"name":"Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12\/14, 61-704 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,7]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"15","DOI":"10.3201\/eid1209.05-0979","article-title":"1918 Influenza: The Mother of All Pandemics","volume":"12","author":"Taubenberger","year":"2006","journal-title":"Emerg. Infect. Dis."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"559","DOI":"10.3389\/fmicb.2018.00559","article-title":"Structural and Functional Motifs in Influenza Virus RNAs","volume":"9","author":"Ferhadian","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_3","first-page":"153","article-title":"Influenza A: Understanding the Viral Life Cycle","volume":"82","author":"Samji","year":"2009","journal-title":"Yale J. Boil. Med."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1581","DOI":"10.3389\/fimmu.2018.01581","article-title":"Influenza A Virus Cell Entry, Replication, Virion Assembly and Movement","volume":"9","author":"Dou","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_5","doi-asserted-by":"crossref","unstructured":"Du, R., Cui, Q., and Rong, L. (2019). Competitive Cooperation of Hemagglutinin and Neuraminidase during Influenza A Virus Entry. Viruses, 11.","DOI":"10.3390\/v11050458"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"a038398","DOI":"10.1101\/cshperspect.a038398","article-title":"Structure and Function of the Influenza Virus Transcription and Replication Machinery","volume":"10","author":"Fodor","year":"2020","journal-title":"Cold Spring Harb. Perspect. Med."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"479","DOI":"10.1038\/nrmicro.2016.87","article-title":"Influenza virus RNA polymerase: Insights into the mechanisms of viral RNA synthesis","volume":"14","author":"Fodor","year":"2016","journal-title":"Nat. Rev. Genet."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"103","DOI":"10.1016\/j.virusres.2017.01.013","article-title":"Structural insights into RNA synthesis by the influenza virus transcription-replication machine","volume":"234","author":"Pflug","year":"2017","journal-title":"Virus Res."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"15041","DOI":"10.1038\/s41598-017-15317-5","article-title":"Influenza virus segment 5 (+)RNA\u2014Secondary structure and new targets for antiviral strategies","volume":"7","author":"Michalak","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-019-40443-7","article-title":"Secondary structure of the segment 5 genomic RNA of influenza A virus and its application for designing antisense oligonucleotides","volume":"9","author":"Michalak","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"7003","DOI":"10.1093\/nar\/gkz318","article-title":"In vivo analysis of influenza A mRNA secondary structures identifies critical regulatory motifs","volume":"47","author":"Simon","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Jiang, T., Nogales, A., Baker, S.F., Martinez-Sobrido, L., and Turner, D.H. (2016). Mutations Designed by Ensemble Defect to Misfold Conserved RNA Structures of Influenza A Segments 7 and 8 Affect Splicing and Attenuate Viral Replication in Cell Culture. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0156906"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"3158","DOI":"10.1002\/j.1460-2075.1994.tb06614.x","article-title":"Structure of influenza virus RNP. I. Influenza virus nucleoprotein melts secondary structure in panhandle RNA and exposes the bases to the solvent","volume":"13","author":"Baudin","year":"1994","journal-title":"EMBO J."},{"key":"ref_14","unstructured":"FDA, U.S. (2020, October 26). Available online: https:\/\/www.fda.gov\/drugs\/information-drug-class\/influenza-flu-antiviral-drugs-and-related-information."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"1438","DOI":"10.3390\/v4091438","article-title":"Evasion of Influenza A Viruses from Innate and Adaptive Immune Responses","volume":"4","author":"Kreijtz","year":"2012","journal-title":"Viruses"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"39","DOI":"10.3389\/fmicb.2019.00039","article-title":"Influenza Virus Neuraminidase Structure and Functions","volume":"10","author":"McAuley","year":"2019","journal-title":"Front. Microbiol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"14659","DOI":"10.1074\/jbc.RA118.004012","article-title":"Structural analyses reveal the mechanism of inhibition of influenza virus NS1 by two antiviral compounds","volume":"293","author":"Kleinpeter","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Lao, J., and Vanet, A. (2017). A New Strategy to Reduce Influenza Escape: Detecting Therapeutic Targets Constituted of Invariance Groups. Viruses, 9.","DOI":"10.3390\/v9030038"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"277","DOI":"10.1089\/nat.2016.0619","article-title":"Antisense Oligonucleotides Targeting Influenza A Segment 8 Genomic RNA Inhibit Viral Replication","volume":"26","author":"Lenartowicz","year":"2016","journal-title":"Nucleic Acid Ther."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Bajan, S., and Hutvagner, G. (2020). RNA-Based Therapeutics: From Antisense Oligonucleotides to miRNAs. Cells, 9.","DOI":"10.3390\/cells9010137"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1016\/j.chembiol.2012.07.011","article-title":"Designing Chemically Modified Oligonucleotides for Targeted Gene Silencing","volume":"19","author":"Deleavey","year":"2012","journal-title":"Chem. Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"475","DOI":"10.1089\/hum.2015.070","article-title":"Oligonucleotide Therapies: The Past and the Present","volume":"26","author":"Lundin","year":"2015","journal-title":"Hum. Gene Ther."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"97","DOI":"10.4149\/av_2013_02_97","article-title":"Role and application of RNA interference in replication of influenza viruses","volume":"57","author":"Betakova","year":"2013","journal-title":"Acta Virol."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1146\/annurev.pharmtox.010909.105654","article-title":"RNA Targeting Therapeutics: Molecular Mechanisms of Antisense Oligonucleotides as a Therapeutic Platform","volume":"50","author":"Bennett","year":"2010","journal-title":"Annu. Rev. Pharmacol. Toxicol."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.antiviral.2011.06.013","article-title":"Packaging signals in the 5\u2032-ends of influenza virus PA, PB1, and PB2 genes as potential targets to develop nucleic-acid based antiviral molecules","volume":"92","author":"Giannecchini","year":"2011","journal-title":"Antivir. Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1177\/135965350801300112","article-title":"In vitro and in vivo protection against the highly pathogenic H5N1 influenza virus by an antisense phosphorothioate oligonucleotide","volume":"13","author":"Duan","year":"2008","journal-title":"Antivir. Ther."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"3724","DOI":"10.1128\/AAC.00644-06","article-title":"Inhibition of Multiple Subtypes of Influenza A Virus in Cell Cultures with Morpholino Oligomers","volume":"50","author":"Ge","year":"2006","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1842","DOI":"10.1021\/acs.bioconjchem.7b00124","article-title":"Delivery System Targeting Hemagglutinin of Influenza Virus A to Facilitate Antisense-Based Anti-H1N1 Therapy","volume":"28","author":"Ding","year":"2017","journal-title":"Bioconjugate Chem."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.bbrc.2007.10.196","article-title":"Inhibition of highly pathogenic avian H5N1 influenza virus replication by RNA oligonucleotides targeting NS1 gene","volume":"365","author":"Wu","year":"2008","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1558","DOI":"10.1016\/j.vaccine.2010.12.088","article-title":"Antisense oligonucleotide inhibits avian influenza virus H5N1 replication by single chain antibody delivery system","volume":"29","author":"Zhang","year":"2011","journal-title":"Vaccine"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"1812","DOI":"10.1166\/jnn.2012.5190","article-title":"Nanocomposites consisting of titanium dioxide nanoparticles and oligonucleotides","volume":"12","author":"Levina","year":"2012","journal-title":"J. Nanosci. Nanotechnol."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep00756","article-title":"High-performance method for specific effect on nucleic acids in cells using TiO2~DNA nanocomposites","volume":"2","author":"Levina","year":"2012","journal-title":"Sci. Rep."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"3949","DOI":"10.1016\/j.vaccine.2010.03.045","article-title":"Generation and characterization of a fusion protein of single-chain fragment variable antibody against hemagglutinin antigen of avian influenza virus and truncated protamine","volume":"28","author":"Zhang","year":"2010","journal-title":"Vaccine"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"2057","DOI":"10.1016\/j.intimp.2011.08.019","article-title":"Antisense oligonucleotides targeting the RNA binding region of the NP gene inhibit replication of highly pathogenic avian influenza virus H5N1","volume":"11","author":"Zhang","year":"2011","journal-title":"Int. Immunopharmacol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"827","DOI":"10.4155\/bio-2016-0289","article-title":"Quantitative determination of AVI-7100 (Radavirsen), a phosphorodiamidate morpholino oligomer (PMOplus\u00ae), in human plasma using LC-MS\/MS","volume":"9","author":"Meng","year":"2017","journal-title":"Bioanalysis"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.antiviral.2017.11.013","article-title":"Prevention and treatment of respiratory viral infections: Presentations on antivirals, traditional therapies and host-directed interventions at the 5th ISIRV Antiviral Group conference","volume":"149","author":"Jiang","year":"2018","journal-title":"Antivir. Res."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"1554","DOI":"10.1128\/JVI.01294-10","article-title":"Inhibition of Influenza Virus Infection in Human Airway Cell Cultures by an Antisense Peptide-Conjugated Morpholino Oligomer Targeting the Hemagglutinin-Activating Protease TMPRSS2","volume":"85","author":"Stein","year":"2011","journal-title":"J. Virol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6543","DOI":"10.1007\/s00253-019-09919-4","article-title":"A LAG3-interfering oligonucleotide acts as an adjuvant to enhance the antibody responses induced by recombinant protein vaccines and inactivated influenza virus vaccines","volume":"103","author":"Li","year":"2019","journal-title":"Appl. Microbiol. Biotechnol."},{"key":"ref_39","doi-asserted-by":"crossref","unstructured":"Huang, D.T.-N., Lu, C.-Y., Shao, P.-L., Chang, L.-Y., Wang, J.-Y., Chang, Y.-H., Lai, M.-J., Chi, Y.-H., and Huang, L. (2017). In vivo inhibition of influenza A virus replication by RNA interference targeting the PB2 subunit via intratracheal delivery. PLoS ONE, 12.","DOI":"10.1371\/journal.pone.0174523"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1038\/gt.2013.49","article-title":"Efficient siRNA transfection to the inner ear through the intact round window by a novel proteidic delivery technology in the chinchilla","volume":"21","author":"Qi","year":"2014","journal-title":"Gene Ther."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"2718","DOI":"10.1073\/pnas.0437841100","article-title":"RNA interference of influenza virus production by directly targeting mRNA for degradation and indirectly inhibiting all viral RNA transcription","volume":"100","author":"Ge","year":"2003","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_42","first-page":"514","article-title":"In vitro validation of self designed \u201cuniversal human Influenza A siRNA\u201d","volume":"53","author":"Jain","year":"2015","journal-title":"Indian J. Exp. Boil."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1016\/j.virol.2016.07.019","article-title":"Inhibition of influenza A virus matrix and nonstructural gene expression using RNA interference","volume":"497","author":"McMillen","year":"2016","journal-title":"Virology"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"e01916-18","DOI":"10.1128\/JVI.01916-18","article-title":"Efficient Inhibition of Avian and Seasonal Influenza A Viruses by a Virus-Specific Dicer-Substrate Small Interfering RNA Swarm in Human Monocyte-Derived Macrophages and Dendritic Cells","volume":"93","author":"Jiang","year":"2019","journal-title":"J. Virol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1016\/j.antiviral.2018.08.003","article-title":"Inhibition of influenza A virus by mixed siRNAs, targeting the PA, NP, and NS genes, delivered by hybrid microcarriers","volume":"158","author":"Brodskaia","year":"2018","journal-title":"Antivir. Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"ra126","DOI":"10.1126\/scisignal.aab3183","article-title":"The microRNA miR-485 targets host and influenza virus transcripts to regulate antiviral immunity and restrict viral replication","volume":"8","author":"Ingle","year":"2015","journal-title":"Sci. Signal."},{"key":"ref_47","first-page":"1","article-title":"Up-regulation of microRNA-203 in influenza A virus infection inhibits viral replication by targeting DR1","volume":"8","author":"Zhang","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fimmu.2018.01541","article-title":"Potential Role of MicroRNAs in the Regulation of Antiviral Responses to Influenza Infection","volume":"9","author":"Nguyen","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1016\/j.omtn.2017.12.016","article-title":"Endogenous Cellular MicroRNAs Mediate Antiviral Defense against Influenza A Virus","volume":"10","author":"Peng","year":"2018","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"509","DOI":"10.1016\/j.omtn.2018.12.014","article-title":"The Downregulation of MicroRNA hsa-miR-340-5p in IAV-Infected A549 Cells Suppresses Viral Replication by Targeting RIG-I and OAS2","volume":"14","author":"Zhao","year":"2019","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"104593","DOI":"10.1016\/j.antiviral.2019.104593","article-title":"Identification of a novel antiviral micro-RNA targeting the NS1 protein of the H1N1 pandemic human influenza virus and a corresponding viral escape mutation","volume":"171","author":"Bavagnoli","year":"2019","journal-title":"Antivir. Res."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s12985-020-1283-9","article-title":"Identification of cellular microRNA miR-188-3p with broad-spectrum anti-influenza A virus activity","volume":"17","author":"Cui","year":"2020","journal-title":"Virol. J."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1038\/nbt.2666","article-title":"MicroRNA-based strategy to mitigate the risk of gain-of-function influenza studies","volume":"31","author":"Langlois","year":"2013","journal-title":"Nat. Biotechnol."},{"key":"ref_54","first-page":"222","article-title":"The chemical repertoire of natural ribozymes","volume":"418","author":"Doudna","year":"2002","journal-title":"Nat. Cell Biol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1016\/S0168-6445(03)00020-2","article-title":"Ribozymes: Recent advances in the development of RNA tools","volume":"27","year":"2003","journal-title":"FEMS Microbiol. Rev."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"11","DOI":"10.2174\/1566523052997541","article-title":"Synthetic Hammerhead Ribozymes as Therapeutic Tools to Control Disease Genes","volume":"5","author":"Citti","year":"2005","journal-title":"Curr. Gene Ther."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"223","DOI":"10.1016\/1074-5521(94)90014-0","article-title":"A DNA enzyme that cleaves RNA","volume":"1","author":"Breaker","year":"1994","journal-title":"Chem. Biol."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"4262","DOI":"10.1073\/pnas.94.9.4262","article-title":"A general purpose RNA-cleaving DNA enzyme","volume":"94","author":"Santoro","year":"1997","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"385","DOI":"10.1002\/jmv.1890420411","article-title":"Ribozyme mediated destruction of influenza A virus in vitro and in vivo","volume":"42","author":"Tang","year":"1994","journal-title":"J. Med. Virol."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1016\/S0166-3542(99)00015-7","article-title":"Inhibition of influenza A virus reproduction by a ribozyme targeted against PB1 mRNA","volume":"42","author":"Lazarev","year":"1999","journal-title":"Antivir. Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1016\/j.antiviral.2010.05.001","article-title":"Potent inhibition of influenza virus replication with novel siRNA-chimeric-ribozyme constructs","volume":"87","author":"Kumar","year":"2010","journal-title":"Antivir. Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1007\/s12033-011-9437-z","article-title":"Nucleic Acid-Mediated Cleavage of M1 Gene of Influenza A Virus Is Significantly Augmented by Antisense Molecules Targeted to Hybridize Close to the Cleavage Site","volume":"51","author":"Kumar","year":"2012","journal-title":"Mol. Biotechnol."},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Motard, J., Rouxel, R.N., Paun, A., Von Messling, V., Bisaillon, M., and Perreault, J.-P. (2011). A Novel Ribozyme-Based Prophylaxis Inhibits Influenza A Virus Replication and Protects from Severe Disease. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0027327"},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/S0014-5793(00)01974-8","article-title":"Inhibition of influenza virus replication in cultured cells by RNA-cleaving DNA enzyme","volume":"481","author":"Toyoda","year":"2000","journal-title":"FEBS Lett."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"69","DOI":"10.1016\/S0014-5793(04)00073-0","article-title":"A new modified DNA enzyme that targets influenza virus A mRNA inhibits viral infection in cultured cells","volume":"560","author":"Takahashi","year":"2004","journal-title":"FEBS Lett."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"836","DOI":"10.1007\/s12033-015-9876-z","article-title":"Potent Intracellular Knock-Down of Influenza A Virus M2 Gene Transcript by DNAzymes Considerably Reduces Viral Replication in Host Cells","volume":"57","author":"Kumar","year":"2015","journal-title":"Mol. Biotechnol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"1781","DOI":"10.1038\/s41564-019-0513-7","article-title":"The structure of the influenza A virus genome","volume":"4","author":"Dadonaite","year":"2019","journal-title":"Nat. Microbiol."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"2197","DOI":"10.1093\/nar\/gkr985","article-title":"A supramolecular assembly formed by influenza A virus genomic RNA segments","volume":"40","author":"Fournier","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"7359","DOI":"10.1016\/j.vaccine.2012.09.079","article-title":"Interaction network linking the human H3N2 influenza A virus genomic RNA segments","volume":"30","author":"Fournier","year":"2012","journal-title":"Vaccine"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"156","DOI":"10.1128\/JVI.74.1.156-163.2000","article-title":"Ultrastructural and Functional Analyses of Recombinant Influenza Virus Ribonucleoproteins Suggest Dimerization of Nucleoprotein during Virus Amplification","volume":"74","author":"Ortega","year":"2000","journal-title":"J. Virol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1038\/nrmicro3367","article-title":"At the centre: Influenza A virus ribonucleoproteins","volume":"13","author":"Eisfeld","year":"2015","journal-title":"Nat. Rev. Genet."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1634","DOI":"10.1126\/science.1228172","article-title":"The Structure of Native Influenza Virion Ribonucleoproteins","volume":"338","author":"Arranz","year":"2012","journal-title":"Science"},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"8140","DOI":"10.1073\/pnas.84.22.8140","article-title":"Genomic RNAs of influenza viruses are held in a circular conformation in virions and in infected cells by a terminal panhandle","volume":"84","author":"Hsu","year":"1987","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_74","first-page":"361","article-title":"Structural insight into cap-snatching and RNA synthesis by influenza polymerase","volume":"516","author":"Reich","year":"2014","journal-title":"Nat. Cell Biol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"10381","DOI":"10.1128\/JVI.00636-13","article-title":"Uncoupling of Influenza A Virus Transcription and Replication through Mutation of the Unpaired Adenosine in the Viral RNA Promoter","volume":"87","author":"Velthuis","year":"2013","journal-title":"J. Virol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1216","DOI":"10.1093\/nar\/gkg214","article-title":"A single-nucleotide natural variation (U4 to C4) in an influenza A virus promoter exhibits a large structural change: Implications for differential viral RNA synthesis by RNA-dependent RNA polymerase","volume":"31","author":"Lee","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"942","DOI":"10.4161\/rna.29730","article-title":"RNA structural constraints in the evolution of the influenza A virus genome NP segment","volume":"11","author":"Gultyaev","year":"2014","journal-title":"RNA Biol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"639","DOI":"10.1038\/ncomms1647","article-title":"Three-dimensional analysis of ribonucleoprotein complexes in influenza A virus","volume":"3","author":"Noda","year":"2012","journal-title":"Nat. Commun."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"12879","DOI":"10.1128\/JVI.02096-13","article-title":"Configuration of Viral Ribonucleoprotein Complexes within the Influenza A Virion","volume":"87","author":"Sugita","year":"2013","journal-title":"J. Virol."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"16604","DOI":"10.1073\/pnas.1314419110","article-title":"A functional sequence-specific interaction between influenza A virus genomic RNA segments","volume":"110","author":"Gavazzi","year":"2013","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"4327","DOI":"10.1042\/BCJ20160651","article-title":"Secondary structure model of the naked segment 7 influenza A virus genomic RNA","volume":"473","author":"Ruszkowska","year":"2016","journal-title":"Biochem. J."},{"key":"ref_82","doi-asserted-by":"crossref","unstructured":"Lenartowicz, E., Kesy, J., Ruszkowska, A., Soszynska-Jozwiak, M., Michalak, P., Moss, W.N., Turner, U.H., Kierzek, E., and Kierzek, E. (2016). Self-Folding of Naked Segment 8 Genomic RNA of Influenza A Virus. PLoS ONE, 11.","DOI":"10.1371\/journal.pone.0148281"},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"991","DOI":"10.1261\/rna.2619511","article-title":"Identification of potential conserved RNA secondary structure throughout influenza A coding regions","volume":"17","author":"Moss","year":"2011","journal-title":"RNA"},{"key":"ref_84","doi-asserted-by":"crossref","unstructured":"Priore, S.F., Moss, W.N., and Turner, D.H. (2012). Influenza A Virus Coding Regions Exhibit Host-Specific Global Ordered RNA Structure. PLoS ONE, 7.","DOI":"10.1371\/journal.pone.0035989"},{"key":"ref_85","doi-asserted-by":"crossref","unstructured":"Priore, S.F., Kierzek, E., Kierzek, E., Baman, J.R., Moss, W.N., Dela-Moss, L.I., and Turner, D.H. (2013). Secondary Structure of a Conserved Domain in the Intron of Influenza A NS1 mRNA. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0070615"},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"1340","DOI":"10.1093\/nar\/28.6.1340","article-title":"Effects of RNA secondary structure on cellular antisense activity","volume":"28","author":"Vickers","year":"2000","journal-title":"Nucleic Acids Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1058","DOI":"10.1093\/bioinformatics\/17.11.1058","article-title":"Concepts to automate the theoretical design of effective antisense oligonucleotides","volume":"17","author":"Far","year":"2001","journal-title":"Bioinformatics"},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"8968","DOI":"10.1093\/nar\/gkx584","article-title":"Genome-wide analysis of influenza viral RNA and nucleoprotein association","volume":"45","author":"Lee","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"4322","DOI":"10.1093\/nar\/gkm437","article-title":"A systematic analysis of the effect of target RNA structure on RNA interference","volume":"35","author":"Westerhout","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"1631","DOI":"10.1261\/rna.546207","article-title":"Effect of target secondary structure on RNAi efficiency","volume":"13","author":"Shao","year":"2007","journal-title":"RNA"},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1016\/j.chembiol.2010.04.011","article-title":"The Efficacy of siRNAs against Hepatitis C Virus Is Strongly Influenced by Structure and Target Site Accessibility","volume":"17","author":"Sagan","year":"2010","journal-title":"Chem. Biol."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"627","DOI":"10.1016\/j.omtn.2019.12.018","article-title":"RNA Secondary Structure Motifs of the Influenza A Virus as Targets for siRNA-Mediated RNA Interference","volume":"19","author":"Piasecka","year":"2020","journal-title":"Mol. Ther. Nucleic Acids"},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"931","DOI":"10.1021\/acs.bioconjchem.9b00039","article-title":"A Short Chemically Modified dsRNA-Binding PNA (dbPNA) Inhibits Influenza Viral Replication by Targeting Viral RNA Panhandle Structure","volume":"30","author":"Kesy","year":"2019","journal-title":"Bioconjugate Chem."},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"663","DOI":"10.1111\/cbdd.12534","article-title":"Targeting Influenza A Virus RNA Promoter","volume":"86","author":"Bottini","year":"2015","journal-title":"Chem. Biol. Drug Des."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"4247","DOI":"10.1016\/j.jmb.2019.04.038","article-title":"Teaching an Old Virus New Tricks: A Review on New Approaches to Study Age-Old Questions in Influenza Biology","volume":"431","author":"Lakdawala","year":"2019","journal-title":"J. Mol. Biol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"673","DOI":"10.1038\/s41573-020-0075-7","article-title":"Advances in oligonucleotide drug delivery","volume":"19","author":"Roberts","year":"2020","journal-title":"Nat. Rev. Drug Discov."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1016\/j.tibtech.2019.09.009","article-title":"Next-Generation Sequencing: An Eye-Opener for the Surveillance of Antiviral Resistance in Influenza","volume":"38","author":"Saelens","year":"2020","journal-title":"Trends Biotechnol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"826","DOI":"10.1016\/j.molcel.2019.09.013","article-title":"Programmable Inhibition and Detection of RNA Viruses Using Cas13","volume":"76","author":"Freije","year":"2019","journal-title":"Mol. Cell"},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"865","DOI":"10.1016\/j.cell.2020.04.020","article-title":"Development of CRISPR as an Antiviral Strategy to Combat SARS-CoV-2 and Influenza","volume":"181","author":"Abbott","year":"2020","journal-title":"Cell"}],"container-title":["Pathogens"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2076-0817\/9\/11\/925\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:30:35Z","timestamp":1760178635000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2076-0817\/9\/11\/925"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,7]]},"references-count":99,"journal-issue":{"issue":"11","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["pathogens9110925"],"URL":"https:\/\/doi.org\/10.3390\/pathogens9110925","relation":{},"ISSN":["2076-0817"],"issn-type":[{"value":"2076-0817","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,7]]}}}