{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,8]],"date-time":"2026-10-08T22:18:37Z","timestamp":1791497917476,"version":"4.3.4"},"reference-count":103,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2022,12,14]],"date-time":"2022-12-14T00:00:00Z","timestamp":1670976000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004281","name":"National Science Center","doi-asserted-by":"publisher","award":["UMO-2019\/35\/D\/NZ6\/01479"],"award-info":[{"award-number":["UMO-2019\/35\/D\/NZ6\/01479"]}],"id":[{"id":"10.13039\/501100004281","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The relationship between conserved structural motifs and their biological function in the virus replication cycle is the interest of many researchers around the world. RNA structure is closely related to RNA function. Therefore, technological progress in high-throughput approaches for RNA structure analysis and the development of new ones are very important. In this mini review, we discuss a few perspectives on the structural elements of viral genomes and some methods used for RNA structure prediction and characterization. Based on the recent literature, we describe several examples of studies concerning the viral genomes, especially severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV). Herein, we emphasize that a better understanding of viral genome architecture allows for the discovery of the structure-function relationship, and as a result, the discovery of new potential antiviral therapeutics.<\/jats:p>","DOI":"10.3390\/ijms232415917","type":"journal-article","created":{"date-parts":[[2022,12,15]],"date-time":"2022-12-15T01:52:30Z","timestamp":1671069150000},"page":"15917","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["Examples of Structural Motifs in Viral Genomes and Approaches for RNA Structure Characterization"],"prefix":"10.3390","volume":"23","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1136-2341","authenticated-orcid":false,"given":"Maria","family":"Nalewaj","sequence":"first","affiliation":[{"name":"Department of RNA Structural Genomics, Institute of Bioorganic Chemistry, Polish Academy of Sciences, Noskowskiego 12\/14, 61-704 Poznan, Poland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5772-0808","authenticated-orcid":false,"given":"Marta","family":"Szabat","sequence":"additional","affiliation":[{"name":"Department of RNA Structural Genomics, 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":[[2022,12,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1221","DOI":"10.1016\/j.ygeno.2020.09.059","article-title":"Genetics and genomics of SARS-CoV-2: A review of the literature with the special focus on genetic diversity and SARS-CoV-2 genome detection","volume":"113","author":"Rahimi","year":"2021","journal-title":"Genomics"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"104260","DOI":"10.1016\/j.meegid.2020.104260","article-title":"Genetic diversity and evolution of SARS-CoV-2","volume":"81","author":"Phan","year":"2020","journal-title":"Infect. Genet. Evol."},{"key":"ref_3","doi-asserted-by":"crossref","unstructured":"ur Rehman, S., Shafique, L., Ihsan, A., and Qingyou, L. (2020). Evolutionary trajectory for the emergence of novel coronavirus SARS-CoV-2. Pathogens, 9.","DOI":"10.3390\/pathogens9030240"},{"key":"ref_4","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_5","doi-asserted-by":"crossref","first-page":"584","DOI":"10.1016\/j.molcel.2020.12.041","article-title":"Comprehensive in vivo secondary structure of the SARS-CoV-2 genome reveals novel regulatory motifs and mechanisms","volume":"81","author":"Huston","year":"2021","journal-title":"Mol. Cell"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.jgg.2012.08.002","article-title":"The role of RNA structure in posttranscriptional regulation of gene expression","volume":"39","author":"Jacobs","year":"2012","journal-title":"J. Genet. Genom."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1146\/annurev-virology-092917-043315","article-title":"Physical and functional analysis of viral RNA genomes by SHAPE","volume":"6","author":"Boerneke","year":"2019","journal-title":"Annu. Rev. Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"755","DOI":"10.1038\/s41589-021-00805-7","article-title":"RNA structure probing uncovers RNA structure-dependent biological functions","volume":"17","author":"Wang","year":"2021","journal-title":"Nat. Chem. Biol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fpls.2018.00671","article-title":"New era of studying RNA secondary structure and its influence on gene regulation in plants","volume":"9","author":"Yang","year":"2018","journal-title":"Front. Plant Sci."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"767","DOI":"10.1016\/j.jmb.2016.01.005","article-title":"Modeling three-dimensional structural motifs of viral IRES","volume":"428","author":"Lozano","year":"2016","journal-title":"J. Mol. Biol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"446","DOI":"10.1016\/j.tim.2014.04.001","article-title":"Selective packaging of the influenza A genome and consequences for genetic reassortment","volume":"22","author":"Gerber","year":"2014","journal-title":"Trends Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"545","DOI":"10.1016\/j.virol.2015.01.014","article-title":"Initiation and regulation of paramyxovirus transcription and replication","volume":"479\u2013480","author":"Noton","year":"2015","journal-title":"Virology"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1016\/j.virusres.2015.02.025","article-title":"The structure and functions of coronavirus genomic 3\u2032 and 5\u2032 ends","volume":"206","author":"Yang","year":"2015","journal-title":"Virus Res."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"533","DOI":"10.3109\/08830185.2010.507828","article-title":"Influenza virus RNA structure: Unique and common features","volume":"29","author":"Gultyaev","year":"2010","journal-title":"Int. Rev. Immunol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"340","DOI":"10.1002\/rmv.1756","article-title":"Unmasking the information encoded as structural motifs of viral RNA genomes: A potential antiviral target","volume":"23","year":"2013","journal-title":"Rev. Med. Virol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1016\/j.virusres.2008.06.006","article-title":"Functional analysis of structural motifs in dicistroviruses","volume":"139","author":"Nakashima","year":"2009","journal-title":"Virus Res."},{"key":"ref_17","doi-asserted-by":"crossref","unstructured":"Khong, A., Bonderoff, J.M., Spriggs, R.V., Tammpere, E., Kerr, C.H., Jackson, T.J., Willis, A.E., and Jan, E. (2016). Temporal regulation of distinct internal ribosome entry sites of the dicistroviridae cricket paralysis virus. Viruses, 8.","DOI":"10.3390\/v8010025"},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"395","DOI":"10.3389\/fmicb.2018.00395","article-title":"Signals involved in regulation of hepatitis C virus RNA genome translation and replication","volume":"9","author":"Niepmann","year":"2018","journal-title":"Front. Microbiol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"43415","DOI":"10.1038\/srep43415","article-title":"The chaperone-like activity of the hepatitis C virus IRES and CRE elements regulates genome dimerization","volume":"7","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"124","DOI":"10.1261\/rna.2950603","article-title":"Structure and function analysis of the poliovirus cis-acting replication element (CRE)","volume":"9","author":"Goodfellow","year":"2003","journal-title":"RNA"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"22952","DOI":"10.1038\/srep22952","article-title":"Identification of novel RNA secondary structures within the hepatitis C virus genome reveals a cooperative involvement in genome packaging","volume":"6","author":"Stewart","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"e01661-20","DOI":"10.1128\/mBio.01661-20","article-title":"Pervasive RNA secondary structure in the genomes of SARS-CoV-2 and other coronaviruses","volume":"11","author":"Simmonds","year":"2020","journal-title":"MBio"},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Simmonds, P., and Azim Ansari, M. (2021). Extensive C->U transition biases in the genomes of a wide range of mammalian RNA viruses; potential associations with transcriptional mutations, damage- or host-mediated editing of viral RNA. PLoS Pathog., 17.","DOI":"10.1371\/journal.ppat.1009596"},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"6316","DOI":"10.1093\/nar\/gkt334","article-title":"Influence of genome-scale RNA structure disruption on the replication of murine norovirus\u2014Similar replication kinetics in cell culture but attenuation of viral fitness in vivo","volume":"41","author":"McFadden","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_25","doi-asserted-by":"crossref","unstructured":"Soszynska-Jozwiak, M., Ruszkowska, A., Kierzek, R., O\u2019leary, C.A., Moss, W.N., and Kierzek, E. (2022). Secondary structure of subgenomic RNA M of SARS-CoV-2. Viruses, 14.","DOI":"10.3390\/v14020322"},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"e12","DOI":"10.1093\/nar\/gkz1124","article-title":"Mapping RNA-capsid interactions and RNA secondary structure within virus particles using next-generation sequencing","volume":"48","author":"Zhou","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"68","DOI":"10.1016\/j.ymeth.2020.04.001","article-title":"Viral RNA structure analysis using DMS-MaPseq","volume":"183","author":"Tomezsko","year":"2020","journal-title":"Methods"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"D183","DOI":"10.1093\/nar\/gkaa880","article-title":"RASP: An atlas of transcriptome-wide RNA secondary structure probing data","volume":"49","author":"Li","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"598","DOI":"10.1038\/nrmicro1704","article-title":"Viral RNA pseudoknots: Versatile motifs in gene expression and replication","volume":"5","author":"Brierley","year":"2007","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"4749","DOI":"10.1038\/s41467-021-25085-6","article-title":"Structural dynamics of single SARS-CoV-2 pseudoknot molecules reveal topologically distinct conformers","volume":"12","author":"Neupane","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_31","first-page":"1","article-title":"SARS-CoV-2 ribosomal frameshifting pseudoknot: Improved secondary structure prediction and detection of inter\u2014Viral structural similarity","volume":"2","author":"Trinity","year":"2020","journal-title":"bioRxiv"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"109223","DOI":"10.1016\/j.vetmic.2021.109223","article-title":"Motif mutations in pseudoknot stem I upstream of start codon in Senecavirus A genome: Impacts on activity of viral IRES and on rescue of recombinant virus","volume":"262","author":"Liu","year":"2021","journal-title":"Vet. Microbiol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"8993","DOI":"10.1093\/nar\/gkx622","article-title":"The IRES5\u2032UTR of the dicistrovirus cricket paralysis virus is a type III IRES containing an essential pseudoknot structure","volume":"45","author":"Gross","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Wang, X., Vlok, M., Flibotte, S., and Jan, E. (2021). Resurrection of a viral internal ribosome entry site from a 700 year old ancient Northwest territories cripavirus. Viruses, 13.","DOI":"10.1101\/2021.01.28.428736"},{"key":"ref_35","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":"Bioconjug. Chem."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"6263","DOI":"10.1128\/JVI.78.12.6263-6270.2004","article-title":"Mutational analysis of the influenza virus cRNA promoter and identification of nucleotides critical for replication","volume":"78","author":"Crow","year":"2004","journal-title":"J. Virol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"13398","DOI":"10.1128\/JVI.06250-11","article-title":"Structural characterization of the viral and cRNA panhandle motifs from the infectious salmon anemia virus","volume":"85","author":"Brinson","year":"2011","journal-title":"J. Virol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"6067","DOI":"10.1128\/JVI.00232-15","article-title":"Influenza A virus panhandle structure is directly involved in RIG-I activation and interferon induction","volume":"89","author":"Liu","year":"2015","journal-title":"J. Virol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"E3335","DOI":"10.1073\/pnas.1406056111","article-title":"Single-molecule FRET reveals a corkscrew RNA structure for the polymerase-bound influenza virus promoter","volume":"111","author":"Tomescu","year":"2014","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"355","DOI":"10.1038\/nature14008","article-title":"Structure of influenza A polymerase bound to the viral RNA promoter","volume":"516","author":"Pflug","year":"2014","journal-title":"Nature"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"4012","DOI":"10.1128\/jvi.69.7.4012-4019.1995","article-title":"Characterization of the RNA-fork model of virion RNA in the initiation of transcription in influenza A virus","volume":"69","author":"Fodor","year":"1995","journal-title":"J. Virol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Gamache, E.R., Doh, J.H., Ritz, J., Laederach, A., Bellaousov, S., Mathews, D.H., and Joan Curcio, M. (2017). Structure-function model for kissing loop interactions that initiate dimerization of Ty1 RNA. Viruses, 9.","DOI":"10.3390\/v9050093"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"3330","DOI":"10.1093\/nar\/gkw061","article-title":"Kissing-loop interaction between 5\u2032 and 3\u2032 ends of tick-borne Langat virus genome \u2018bridges the gap\u2019 between mosquito-and tick-borne flaviviruses in mechanisms of viral RNA cyclization: Applications for virus attenuation and vaccine development","volume":"44","author":"Tsetsarkin","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_44","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_45","doi-asserted-by":"crossref","first-page":"107823","DOI":"10.1016\/j.celrep.2020.107823","article-title":"Mapping of influenza virus RNA-RNA interactions reveals a flexible network","volume":"31","author":"Kanarek","year":"2020","journal-title":"Cell Rep."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1016\/j.omtn.2020.12.030","article-title":"Inhibition of Zika virus replication by G-quadruplex-binding ligands","volume":"23","author":"Majee","year":"2021","journal-title":"Mol. Ther.-Nucleic Acids"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"1445","DOI":"10.1021\/acsinfecdis.0c00793","article-title":"Targeting a potential G-quadruplex forming sequence found in the West Nile virus genome by complementary gamma-peptide nucleic acid oligomers","volume":"7","author":"Sarkar","year":"2021","journal-title":"ACS Infect. Dis."},{"key":"ref_48","doi-asserted-by":"crossref","unstructured":"Tomaszewska, M., Szabat, M., Zieli\u0144ska, K., and Kierzek, R. (2021). Identification and structural aspects of G-quadruplex-forming sequences from the influenza A virus genome. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22116031"},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1698","DOI":"10.1093\/nar\/gkm020","article-title":"Resolving fast and slow motions in the internal loop containing stem-loop 1 of HIV-1 that are modulated by Mg2+ binding: Role in the kissing-duplex structural transition","volume":"35","author":"Sun","year":"2007","journal-title":"Nucleic Acids Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"1150","DOI":"10.1093\/bib\/bbaa114","article-title":"Discovery of G-quadruplex-forming sequences in SARS-CoV-2","volume":"22","author":"Ji","year":"2021","journal-title":"Brief. Bioinform."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"262","DOI":"10.1016\/j.chembiol.2014.12.013","article-title":"A potassium ion-dependent RNA structural switch regulates human pre-miRNA 92b maturation","volume":"22","author":"Dassanayake","year":"2015","journal-title":"Chem. Biol."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Real-Hohn, A., Groznica, M., Kontaxis, G., Zhu, R., Chaves, O., Vazquez, L., Hinterdorfer, P., Blaas, D., and Kowalski, H. (2021). Targeting G-quadruplexes in the rhinovirus genome by Pyridostatin inhibits uncoating and highlights a critical role for sodium ions. Res. Sq.","DOI":"10.21203\/rs.3.rs-646190\/v1"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"W471","DOI":"10.1093\/nar\/gkt290","article-title":"RNAstructure: Web servers for RNA secondary structure prediction and analysis","volume":"41","author":"Bellaousov","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"70","DOI":"10.1093\/nar\/gkn188","article-title":"The Vienna RNA Websuite","volume":"36","author":"Gruber","year":"2008","journal-title":"Nucleic Acids Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/1748-7188-6-26","article-title":"ViennaRNA Package 2.0","volume":"6","author":"Lorenz","year":"2011","journal-title":"Algorithms Mol. Biol."},{"key":"ref_56","first-page":"3","article-title":"UNAFold: Software for nucleic acid folding and hybridization","volume":"Volume 453","author":"Keith","year":"2008","journal-title":"Bioinformatics, Volume II: Structure, Function and Applications"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"3406","DOI":"10.1093\/nar\/gkg595","article-title":"Mfold web server for nucleic acid folding and hybridization prediction","volume":"31","author":"Zuker","year":"2003","journal-title":"Nucleic Acids Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"e6136","DOI":"10.7717\/peerj.6136","article-title":"ScanFold: An approach for genome-wide discovery of local RNA structural elements-applications to Zika virus and HIV","volume":"6","author":"Andrews","year":"2018","journal-title":"PeerJ"},{"key":"ref_59","doi-asserted-by":"crossref","unstructured":"Harmanci, A.O., Sharma, G., and Mathews, D.H. (2011). TurboFold: Iterative probabilistic estimation of secondary structures for multiple RNA sequences. BMC Bioinform., 12.","DOI":"10.1186\/1471-2105-12-108"},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"143","DOI":"10.3389\/fgene.2019.00143","article-title":"DMFold: A novel method to predict RNA secondary structure with pseudoknots based on deep learning and improved base pair maximization principle","volume":"10","author":"Wang","year":"2019","journal-title":"Front. Genet."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1007\/s41048-020-00114-x","article-title":"Prediction of RNA secondary structure with pseudoknots using coupled deep neural networks","volume":"6","author":"Mao","year":"2020","journal-title":"Biophys. Rep."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Mao, K., Wang, J., and Xiao, Y. (2022). Length-dependent deep learning model for RNA secondary structure prediction. Molecules, 27.","DOI":"10.3390\/molecules27031030"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1038\/s41467-021-21194-4","article-title":"RNA secondary structure prediction using deep learning with thermodynamic integration","volume":"12","author":"Sato","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"lqab127","DOI":"10.1093\/nargab\/lqab127","article-title":"Prediction and analysis of functional RNA structures within the integrative genomics viewer","volume":"4","author":"Rouse","year":"2022","journal-title":"NAR Genom. Bioinforma."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"937","DOI":"10.1261\/rna.076141.120","article-title":"RNA genome conservation and secondary structure in SARS-CoV-2 and SARS-related viruses: A first look","volume":"26","author":"Rangan","year":"2020","journal-title":"Rna"},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"162","DOI":"10.1186\/s12985-019-1271-0","article-title":"Changes in RNA secondary structure affect NS1 protein expression during early stage influenza virus infection","volume":"16","author":"Baranovskaya","year":"2019","journal-title":"Virol. J."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"e9882","DOI":"10.7717\/peerj.9882","article-title":"A survey of RNA secondary structural propensity encoded within human herpesvirus genomes: Global comparisons and local motifs","volume":"8","author":"Andrews","year":"2020","journal-title":"PeerJ"},{"key":"ref_68","first-page":"1","article-title":"An in silico map of the SARS-CoV-2 RNA structurome","volume":"3","author":"Andrews","year":"2020","journal-title":"bioRxiv"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.virusres.2018.11.005","article-title":"SilentMutations (SIM): A tool for analyzing long-range RNA\u2013RNA interactions in viral genomes and structured RNAs","volume":"260","author":"Ibrahim","year":"2019","journal-title":"Virus Res."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.3389\/fimmu.2018.02097","article-title":"RNA structure\u2014A neglected puppet master for the evolution of virus and host immunity","volume":"9","author":"Smyth","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"5075","DOI":"10.1093\/nar\/gkt203","article-title":"Structural complexity of Dengue virus untranslated regions: Cis-acting RNA motifs and pseudoknot interactions modulating functionality of the viral genome","volume":"41","author":"Teramoto","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"W663","DOI":"10.1093\/nar\/gkac218","article-title":"RNAspider: A webserver to analyze entanglements in RNA 3D structures","volume":"50","author":"Luwanski","year":"2022","journal-title":"Nucleic Acids Res."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"801","DOI":"10.1016\/j.humimm.2021.02.012","article-title":"Next-generation sequencing technologies: An overview","volume":"82","author":"Hu","year":"2021","journal-title":"Hum. Immunol."},{"key":"ref_74","doi-asserted-by":"crossref","unstructured":"Rasmussen, T.B., Boniotti, M.B., Papetti, A., Grasland, B., Frossard, J.P., Dastjerdi, A., Hulst, M., Hanke, D., Pohlmann, A., and Blome, S. (2018). Full-length genome sequences of porcine epidemic diarrhoea virus strain CV777; Use of NGS to analyse genomic and sub-genomic RNAs. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0193682"},{"key":"ref_75","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_76","doi-asserted-by":"crossref","first-page":"4582","DOI":"10.1080\/07391102.2020.1778535","article-title":"Structure-based virtual screening and molecular dynamics simulation of SARS-CoV-2 Guanine-N7 methyltransferase (nsp14) for identifying antiviral inhibitors against COVID-19","volume":"39","author":"Selvaraj","year":"2021","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"107241","DOI":"10.1016\/j.compbiolchem.2020.107241","article-title":"Structure-based virtual screening of influenza virus RNA polymerase inhibitors from natural compounds: Molecular dynamics simulation and MM-GBSA calculation","volume":"85","author":"Jin","year":"2020","journal-title":"Comput. Biol. Chem."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"1512","DOI":"10.1080\/07391102.2015.1081620","article-title":"Identification of dengue viral RNA-dependent RNA polymerase inhibitor using computational fragment-based approaches and molecular dynamics study","volume":"34","author":"Anusuya","year":"2016","journal-title":"J. Biomol. Struct. Dyn."},{"key":"ref_79","doi-asserted-by":"crossref","unstructured":"Cihlova, B., Huskova, A., B\u00f6serle, J., Nencka, R., Boura, E., and Silhan, J. (2021). High-throughput fluorescent assay for inhibitor screening of proteases from RNA viruses. Molecules, 26.","DOI":"10.3390\/molecules26133792"},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"3193","DOI":"10.3390\/molecules25143193","article-title":"High throughput virtual screening to discover inhibitors of the main protease of the coronavirus SARS-CoV-2","volume":"25","author":"Olubiy","year":"2020","journal-title":"Molecules"},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"e00023-19","DOI":"10.1128\/JVI.00023-19","article-title":"High-throughput screening and identification of potent broad-spectrum inhibitors of coronaviruses","volume":"93","author":"Shen","year":"2019","journal-title":"J. Virol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"eaaz8201","DOI":"10.1126\/sciadv.aaz8201","article-title":"Discovery of direct-acting antiviral agents with a graphene-based fluorescent nanosensor","volume":"6","author":"Park","year":"2020","journal-title":"Sci. Adv."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"148","DOI":"10.3390\/covid2020011","article-title":"A comprehensive review of drug repurposing strategies against known drug targets of COVID-19","volume":"2","author":"Khataniar","year":"2022","journal-title":"Covid"},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"105013","DOI":"10.1016\/j.antiviral.2021.105013","article-title":"Identification of a novel inhibitor targeting influenza A virus group 2 hemagglutinins","volume":"186","author":"Du","year":"2021","journal-title":"Antiviral Res."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1007\/s13238-021-00836-9","article-title":"High-throughput screening identifies established drugs as SARS-CoV-2 PLpro inhibitors","volume":"12","author":"Zhao","year":"2021","journal-title":"Protein Cell"},{"key":"ref_86","first-page":"341","article-title":"Whole genome analysis and targeted drug discovery using computational methods and high throughput screening tools for emerged novel coronavirus (2019-nCoV)","volume":"3","author":"Manikyam","year":"2020","journal-title":"J. Pharm. Drug Res."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"476","DOI":"10.1007\/s12250-020-00316-0","article-title":"Generation of a stable GFP-reporter Zika virus system for high-throughput screening of Zika virus inhibitors","volume":"36","author":"Zhang","year":"2021","journal-title":"Virol. Sin."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"198388","DOI":"10.1016\/j.virusres.2021.198388","article-title":"Discovery of an imidazonaphthyridine and a riminophenazine as potent anti-Zika virus agents through a replicon-based high-throughput screening","volume":"299","author":"Fernandes","year":"2021","journal-title":"Virus Res."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"101245","DOI":"10.1016\/j.jbc.2021.101245","article-title":"Universal and strain specific structure features of segment 8 genomic RNA of influenza A virus-application of 4-thiouridine photocrosslinking","volume":"297","author":"Pszczola","year":"2021","journal-title":"J. Biol. Chem."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"12415","DOI":"10.1093\/nar\/gkaa1013","article-title":"Secondary structure determination of conserved SARS-CoV-2 RNA elements by NMR spectroscopy","volume":"48","author":"Wacker","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1181","DOI":"10.1038\/nprot.2018.010","article-title":"In-cell RNA structure probing with SHAPE-MaP","volume":"13","author":"Smola","year":"2018","journal-title":"Nat. Protoc."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"e00701","DOI":"10.1128\/JVI.00701-20","article-title":"Using SHAPE-MaP to model RNA secondary structure and identify 3\u2032UTR variation in Chikungunya virus","volume":"94","author":"Madden","year":"2020","journal-title":"J. Virol."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"438","DOI":"10.1038\/s41586-020-2253-5","article-title":"Determination of RNA structural diversity and its role in HIV-1 RNA splicing","volume":"582","author":"Tomezsko","year":"2020","journal-title":"Nature"},{"key":"ref_94","doi-asserted-by":"crossref","first-page":"5113","DOI":"10.1038\/s41467-021-25357-1","article-title":"Comprehensive mapping of SARS-CoV-2 interactions in vivo reveals functional virus-host interactions","volume":"12","author":"Yang","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"11513","DOI":"10.1073\/pnas.1716689115","article-title":"Pervasive tertiary structure in the dengue virus RNA genome","volume":"115","author":"Dethoff","year":"2018","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"231","DOI":"10.1038\/s41589-020-0477-1","article-title":"Cryo-electron microscopy for the study of virus assembly","volume":"16","author":"Luque","year":"2020","journal-title":"Nat. Chem. Biol."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"610","DOI":"10.1111\/mmi.14820","article-title":"From cells to atoms: Cryo-EM as an essential tool to investigate pathogen biology, host\u2013pathogen interaction, and drug discovery","volume":"117","author":"Shepherd","year":"2022","journal-title":"Mol. Microbiol."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"747","DOI":"10.1038\/s41594-021-00653-y","article-title":"Cryo-EM and antisense targeting of the 28-kDa frameshift stimulation element from the SARS-CoV-2 RNA genome","volume":"28","author":"Zhang","year":"2021","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_99","doi-asserted-by":"crossref","first-page":"137","DOI":"10.1038\/s41586-018-0630-0","article-title":"Cryo-EM structure of the Ebola virus nucleoprotein\u2013RNA complex at 3.6 \u00c5 resolution","volume":"563","author":"Sugita","year":"2018","journal-title":"Nature"},{"key":"ref_100","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1038\/s42003-021-02362-0","article-title":"Structural plasticity of mumps virus nucleocapsids with cryo-EM structures","volume":"4","author":"Shan","year":"2021","journal-title":"Commun. Biol."},{"key":"ref_101","doi-asserted-by":"crossref","first-page":"3801","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_102","doi-asserted-by":"crossref","first-page":"1944","DOI":"10.1038\/s41591-022-01908-x","article-title":"Programmable antivirals targeting critical conserved viral RNA secondary structures from influenza A virus and SARS-CoV-2","volume":"28","author":"Hagey","year":"2022","journal-title":"Nat. Med."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1016\/j.chom.2020.04.021","article-title":"The challenges of vaccine development against a new virus during a pandemic","volume":"27","author":"Diamond","year":"2020","journal-title":"Cell Host Microbe"}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/24\/15917\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T01:41:20Z","timestamp":1760146880000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/23\/24\/15917"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,12,14]]},"references-count":103,"journal-issue":{"issue":"24","published-online":{"date-parts":[[2022,12]]}},"alternative-id":["ijms232415917"],"URL":"https:\/\/doi.org\/10.3390\/ijms232415917","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2022,12,14]]}}}