{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T09:23:49Z","timestamp":1780478629896,"version":"3.54.1"},"reference-count":93,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T00:00:00Z","timestamp":1614902400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006668","name":"Fondo para la Investigaci\u00f3n Cient\u00edfica y Tecnol\u00f3gica","doi-asserted-by":"publisher","award":["PICT 2017-0976"],"award-info":[{"award-number":["PICT 2017-0976"]}],"id":[{"id":"10.13039\/501100006668","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100009573","name":"Universidad Nacional de Rosario","doi-asserted-by":"publisher","award":["BIO573"],"award-info":[{"award-number":["BIO573"]}],"id":[{"id":"10.13039\/100009573","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>The Coronavirus Disease 2019 (COVID-19) pandemic has become a global health emergency with no effective medical treatment and with incipient vaccines. It is caused by a new positive-sense RNA virus called severe acute respiratory syndrome-related coronavirus 2 (SARS-CoV-2). G-quadruplexes (G4s) are nucleic acid secondary structures involved in the control of a variety of biological processes including viral replication. Using several G4 prediction tools, we identified highly putative G4 sequences (PQSs) within the positive-sense (+gRNA) and negative-sense (\u2212gRNA) RNA strands of SARS-CoV-2 conserved in related betacoronaviruses. By using multiple biophysical techniques, we confirmed the formation of two G4s in the +gRNA and provide the first evidence of G4 formation by two PQSs in the \u2212gRNA of SARS-CoV-2. Finally, biophysical and molecular approaches were used to demonstrate for the first time that CNBP, the main human cellular protein bound to SARS-CoV-2 RNA genome, binds and promotes the unfolding of G4s formed by both strands of SARS-CoV-2 RNA genome. Our results suggest that G4s found in SARS-CoV-2 RNA genome and its negative-sense replicative intermediates, as well as the cellular proteins that interact with them, are relevant factors for viral genes expression and replication cycle, and may constitute interesting targets for antiviral drugs development.<\/jats:p>","DOI":"10.3390\/ijms22052614","type":"journal-article","created":{"date-parts":[[2021,3,5]],"date-time":"2021-03-05T05:03:15Z","timestamp":1614920595000},"page":"2614","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":45,"title":["CNBP Binds and Unfolds In Vitro G-Quadruplexes Formed in the SARS-CoV-2 Positive and Negative Genome Strands"],"prefix":"10.3390","volume":"22","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2218-9364","authenticated-orcid":false,"given":"Georgina","family":"Bezzi","sequence":"first","affiliation":[{"name":"Instituto de Biolog\u00eda Molecular y Celular de Rosario (IBR), Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Universidad Nacional de Rosario (UNR), Ocampo y Esmeralda, Rosario S200EZP, Santa Fe, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ernesto J.","family":"Piga","sequence":"additional","affiliation":[{"name":"Instituto de Biolog\u00eda Molecular y Celular de Rosario (IBR), Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Universidad Nacional de Rosario (UNR), Ocampo y Esmeralda, Rosario S200EZP, Santa Fe, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andr\u00e9s","family":"Binolfi","sequence":"additional","affiliation":[{"name":"Instituto de Biolog\u00eda Molecular y Celular de Rosario (IBR), Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Universidad Nacional de Rosario (UNR), Ocampo y Esmeralda, Rosario S200EZP, Santa Fe, Argentina"},{"name":"Plataforma Argentina de Biolog\u00eda Estructural y Metabol\u00f3mica (PLABEM), Ocampo y Esmeralda, Rosario S200EZP, Santa Fe, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0454-1424","authenticated-orcid":false,"given":"Pablo","family":"Armas","sequence":"additional","affiliation":[{"name":"Instituto de Biolog\u00eda Molecular y Celular de Rosario (IBR), Consejo Nacional de Investigaciones Cient\u00edficas y T\u00e9cnicas (CONICET), Universidad Nacional de Rosario (UNR), Ocampo y Esmeralda, Rosario S200EZP, Santa Fe, Argentina"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,3,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"270","DOI":"10.1038\/s41586-020-2012-7","article-title":"A pneumonia outbreak associated with a new coronavirus of probable bat origin","volume":"579","author":"Zhou","year":"2020","journal-title":"Nature"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"536","DOI":"10.1038\/s41564-020-0695-z","article-title":"The species Severe acute respiratory syndrome-related coronavirus: Classifying 2019-nCoV and naming it SARS-CoV-2","volume":"5","author":"Gorbalenya","year":"2020","journal-title":"Nat. Microbiol."},{"key":"ref_3","first-page":"3","article-title":"Properties of coronavirus and SARS-CoV-2","volume":"42","author":"Malik","year":"2020","journal-title":"Malays. J. Pathol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1394","DOI":"10.1126\/science.1085952","article-title":"Characterization of a novel coronavirus associated with severe acute respiratory syndrome","volume":"300","author":"Rota","year":"2003","journal-title":"Science"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"35","DOI":"10.18683\/germs.2019.1155","article-title":"Middle east respiratory syndrome coronavirus (MERS-COV): A review","volume":"9","author":"Ramadan","year":"2019","journal-title":"GERMS"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"565","DOI":"10.1016\/S0140-6736(20)30251-8","article-title":"Genomic characterisation and epidemiology of 2019 novel coronavirus: Implications for virus origins and receptor binding","volume":"395","author":"Lu","year":"2020","journal-title":"Lancet"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"e14","DOI":"10.1016\/S2666-5247(20)30004-5","article-title":"Comparative tropism, replication kinetics, and cell damage profiling of SARS-CoV-2 and SARS-CoV with implications for clinical manifestations, transmissibility, and laboratory studies of COVID-19: An observational study","volume":"1","author":"Chu","year":"2020","journal-title":"Lancet Microbe"},{"key":"ref_8","doi-asserted-by":"crossref","unstructured":"Mousavizadeh, L., and Ghasemi, S. (2020). Genotype and phenotype of COVID-19: Their roles in pathogenesis. J. Microbiol. Immunol. Infect., in press.","DOI":"10.1016\/j.jmii.2020.03.022"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1007\/978-1-4939-2438-7_1","article-title":"Coronaviruses: An overview of their replication and pathogenesis","volume":"Volume 1282","author":"Fehr","year":"2015","journal-title":"Coronaviruses: Methods and Protocols"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"265","DOI":"10.1146\/annurev-virology-100114-055218","article-title":"Continuous and discontinuous RNA synthesis in coronaviruses","volume":"2","author":"Sola","year":"2015","journal-title":"Annu. Rev. Virol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"360","DOI":"10.1038\/nrmicro.2016.45","article-title":"Viral evasion of intracellular DNA and RNA sensing","volume":"14","author":"Chan","year":"2016","journal-title":"Nat. Rev. Microbiol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"1036","DOI":"10.1016\/j.cell.2020.04.026","article-title":"Imbalanced host response to SARS-CoV-2 drives development of COVID-19","volume":"181","author":"Liu","year":"2020","journal-title":"Cell"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Emanuel, W., Kirstin, M., Vedran, F., Asija, D., Theresa, G.L., Roberto, A., Filippos, K., David, K., Salah, A., and Christopher, B. (2020). Bulk and single-cell gene expression profiling of SARS-CoV-2 infected human cell lines identifies molecular targets for therapeutic intervention. bioRxiv.","DOI":"10.1101\/2020.05.05.079194"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"685","DOI":"10.1016\/j.cell.2020.06.034","article-title":"The global phosphorylation landscape of SARS-CoV-2 infection","volume":"182","author":"Bouhaddou","year":"2020","journal-title":"Cell"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1038\/s41586-020-2332-7","article-title":"Proteomics of SARS-CoV-2-infected host cells reveals therapy targets","volume":"583","author":"Bojkova","year":"2020","journal-title":"Nature"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"164","DOI":"10.1016\/j.molcel.2020.08.006","article-title":"Growth factor receptor signaling inhibition prevents SARS-CoV-2 replication","volume":"80","author":"Klann","year":"2020","journal-title":"Mol. Cell"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1038\/s41586-020-2286-9","article-title":"A SARS-CoV-2 protein interaction map reveals targets for drug repurposing","volume":"583","author":"Gordon","year":"2020","journal-title":"Nature"},{"key":"ref_18","doi-asserted-by":"crossref","unstructured":"Gordon, D.E., Hiatt, J., Bouhaddou, M., Rezelj, V.V., Ulferts, S., Braberg, H., Jureka, A.S., Obernier, K., Guo, J.Z., and Batra, J. (2020). Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science, 370.","DOI":"10.1126\/science.abe9403"},{"key":"ref_19","doi-asserted-by":"crossref","unstructured":"Schmidt, N., Lareau, C.A., Keshishian, H., Ganskih, S., Schneider, C., Hennig, T., Melanson, R., Werner, S., Wei, Y., and Zimmer, M. (2020). The SARS-CoV-2 RNA\u2013protein interactome in infected human cells. Nat. Microbiol.","DOI":"10.1038\/s41564-020-00846-z"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2097","DOI":"10.3389\/fimmu.2018.02097","article-title":"RNA structure-a neglected puppet master for the evolution of virus and host immunity","volume":"9","author":"Smyth","year":"2018","journal-title":"Front. Immunol."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1038\/s41580-020-0236-x","article-title":"The regulation and functions of DNA and RNA G-quadruplexes","volume":"21","author":"Varshney","year":"2020","journal-title":"Nat. Rev. Mol. Cell Biol."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"3862","DOI":"10.1093\/nar\/gkz179","article-title":"Whole genome experimental maps of DNA G-quadruplexes in multiple species","volume":"47","author":"Marsico","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Bartas, M., Cutov\u00e1, M., Br\u00e1zda, V., Kaura, P., \u0160t\u2019Astn\u00fd, J., Kolomazn\u00edk, J., Coufal, J., Goswami, P., \u010cerve\u0148, J., and Pe\u010dinka, P. (2019). The presence and localization of G-quadruplex forming sequences in the domain of bacteria. Molecules, 24.","DOI":"10.3390\/molecules24091711"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Br\u00e1zda, V., Luo, Y., Bartas, M., Kaura, P., Porubiakov\u00e1, O., \u0160\u0165astn\u00fd, J., Pe\u010dinka, P., Verga, D., Da Cunha, V., and Takahashi, T.S. (2020). G-Quadruplexes in the archaea domain. Biomolecules, 10.","DOI":"10.3390\/biom10091349"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"49","DOI":"10.1146\/annurev-micro-090817-062629","article-title":"Above and beyond watson and crick: Guanine quadruplex structures and microbes","volume":"72","author":"Seifert","year":"2018","journal-title":"Annu. Rev. Microbiol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"148","DOI":"10.1016\/j.tim.2018.08.011","article-title":"G-Quadruplexes: More than just a kink in microbial genomes","volume":"27","author":"Saranathan","year":"2018","journal-title":"Trends Microbiol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"e1006675","DOI":"10.1371\/journal.pcbi.1006675","article-title":"G-Quadruplex forming sequences in the genome of all known human viruses: A comprehensive guide","volume":"14","author":"Lavezzo","year":"2018","journal-title":"PLoS Comput. Biol."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"3270","DOI":"10.1093\/nar\/gky187","article-title":"Survey and summary G-quadruplexes and G-quadruplex ligands: Targets and tools in antiviral therapy","volume":"46","author":"Ruggiero","year":"2018","journal-title":"Nucleic Acids Res."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/bs.armc.2020.04.001","article-title":"Viral G-quadruplexes: New frontiers in virus pathogenesis and antiviral therapy","volume":"Volume 54","author":"Ruggiero","year":"2020","journal-title":"Annual Reports in Medicinal Chemistry"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Ji, D., Juhas, M., Tsang, C.M., Kwok, C.K., Li, Y., and Zhang, Y. (2020). Discovery of G-quadruplex-forming sequences in SARS-CoV-2. Brief. Bioinform., bbaa114.","DOI":"10.1093\/bib\/bbaa114"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"941","DOI":"10.1007\/s40265-020-01321-z","article-title":"The G-quadruplex\/helicase world as a potential antiviral approach against COVID-19","volume":"80","author":"Panera","year":"2020","journal-title":"Drugs"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"587829","DOI":"10.3389\/fgene.2020.587829","article-title":"Whole genome identification of potential G-quadruplexes and analysis of the G-quadruplex binding domain for SARS-CoV-2","volume":"11","author":"Zhang","year":"2020","journal-title":"Front. Genet."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.3389\/fmicb.2020.01583","article-title":"In-Depth bioinformatic analyses of nidovirales including human SARS-CoV-2, SARS-CoV, MERS-CoV viruses suggest important roles of non-canonical nucleic acid structures in their lifecycles","volume":"11","author":"Bartas","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_34","doi-asserted-by":"crossref","unstructured":"Belmonte-Reche, E., Serrano-Chac\u00f3n, I., Gonzalez, C., Gallo, J., and Ba\u00f1obre-L\u00f3pez, M. (2020). Exploring G and C-quadruplex structures as potential targets against the severe acute respiratory syndrome coronavirus 2. bioRxiv.","DOI":"10.1101\/2020.08.19.257493"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"432","DOI":"10.1002\/anie.202011419","article-title":"Targeting RNA G-quadruplex in SARS-CoV-2: A promising therapeutic target for COVID-19?","volume":"60","author":"Zhao","year":"2021","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"567317","DOI":"10.3389\/fmicb.2020.567317","article-title":"G-Quadruplexes are present in human coronaviruses including SARS-CoV-2","volume":"11","author":"Cui","year":"2020","journal-title":"Front. Microbiol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"16315","DOI":"10.1002\/chem.201803530","article-title":"RNA versus DNA G-quadruplex: The origin of increased stability","volume":"24","author":"Zaccaria","year":"2018","journal-title":"Chem. Eur. J."},{"key":"ref_38","doi-asserted-by":"crossref","unstructured":"Perrone, R., Nadai, M., Poe, J.A., Frasson, I., Palumbo, M., Pal\u00f9, G., Smithgall, T.E., and Richter, S.N. (2013). Formation of a unique cluster of G-quadruplex structures in the HIV-1 nef coding region: Implications for antiviral activity. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0073121"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1038\/nchembio.1479","article-title":"G-Quadruplexes regulate Epstein-Barr virus-encoded nuclear antigen 1 mRNA translation","volume":"10","author":"Murat","year":"2014","journal-title":"Nat. Chem. Biol."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1021\/acsinfecdis.6b00109","article-title":"Zika virus genomic RNA possesses conserved G-quadruplexes characteristic of the flaviviridae family","volume":"2","author":"Fleming","year":"2016","journal-title":"ACS Infect. Dis."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.1016\/j.chembiol.2016.07.019","article-title":"Chemical targeting of a G-quadruplex RNA in the Ebola Virus L. Gene","volume":"23","author":"Wang","year":"2016","journal-title":"Cell Chem. Biol."},{"key":"ref_42","doi-asserted-by":"crossref","unstructured":"Zahin, M., Dean, W.L., Ghim, S., Joh, J., Gray, R.D., Khanal, S., Bossart, G.D., Mignucci-Giannoni, A.A., Rouchka, E.C., and Jenson, A.B. (2018). Identification of G-quadruplex forming sequences in three manatee papillomaviruses. PLoS ONE, 13.","DOI":"10.1371\/journal.pone.0195625"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"1477","DOI":"10.1038\/s41598-020-58406-8","article-title":"Identification and characterization of two conserved G-quadruplex forming motifs in the Nipah virus genome and their interaction with G-quadruplex specific ligands","volume":"10","author":"Majee","year":"2020","journal-title":"Sci. Rep."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"816","DOI":"10.1080\/15476286.2020.1731664","article-title":"G2-Quadruplex in the 3\u2019UTR of IE180 regulates pseudorabies virus replication by enhancing gene expression","volume":"17","author":"Zhang","year":"2020","journal-title":"RNA Biol."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"W676","DOI":"10.1093\/nar\/gkl253","article-title":"QGRS mapper: A web-based server for predicting G-quadruplexes in nucleotide sequences","volume":"34","author":"Kikin","year":"2006","journal-title":"Nucleic Acids Res."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"2584","DOI":"10.1093\/bioinformatics\/btz928","article-title":"Pqsfinder web: G-quadruplex prediction using optimized pqsfinder algorithm","volume":"36","author":"Labudova","year":"2020","journal-title":"Bioinformatics"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.biochi.2018.06.002","article-title":"G4RNA screener web server: User focused interface for RNA G-quadruplex prediction","volume":"151","author":"Garant","year":"2018","journal-title":"Biochimie"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"1209","DOI":"10.1093\/nar\/gkt904","article-title":"New scoring system to identify RNA G-quadruplex folding","volume":"42","author":"Beaudoin","year":"2014","journal-title":"Nucleic Acids Res."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1746","DOI":"10.1093\/nar\/gkw006","article-title":"Re-Evaluation of G-quadruplex propensity with G4Hunter","volume":"44","author":"Bedrat","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"3532","DOI":"10.1093\/bioinformatics\/btx498","article-title":"Motif independent identification of potential RNA G-quadruplexes by G4RNA screener","volume":"33","author":"Garant","year":"2017","journal-title":"Bioinformatics"},{"key":"ref_51","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_52","doi-asserted-by":"crossref","first-page":"33","DOI":"10.1002\/gch2.1018","article-title":"Data, disease and diplomacy: GISAID\u2019s innovative contribution to global health","volume":"1","author":"Elbe","year":"2017","journal-title":"Glob. Chall."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"5749","DOI":"10.1093\/nar\/gkp590","article-title":"The disruptive positions in human G-quadruplex motifs are less polymorphic and more conserved than their neutral counterparts","volume":"37","author":"Nakken","year":"2009","journal-title":"Nucleic Acids Res."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"3800","DOI":"10.1093\/nar\/gkr1258","article-title":"Quadruplex-single nucleotide polymorphisms (Quad-SNP) influence gene expression difference among individuals","volume":"40","author":"Baral","year":"2012","journal-title":"Nucleic Acids Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"459","DOI":"10.1038\/s10038-019-0578-4","article-title":"Obstetric complication-associated ANXA5 promoter polymorphisms may affect gene expression via DNA secondary structures","volume":"64","author":"Inagaki","year":"2019","journal-title":"J. Hum. Genet."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"7022","DOI":"10.1093\/nar\/gkq557","article-title":"5\u2032-UTR G-quadruplex structures acting as translational repressors","volume":"38","author":"Beaudoin","year":"2010","journal-title":"Nucleic Acids Res."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/s41598-017-00739-y","article-title":"Cancer-Associated noncoding mutations affect RNA G-quadruplex-mediated regulation of gene expression","volume":"7","author":"Zeraati","year":"2017","journal-title":"Sci. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","unstructured":"Lee, D.S.M., Ghanem, L.R., and Barash, Y. (2020). Integrative analysis reveals RNA G-quadruplexes in UTRs are selectively constrained and enriched for functional associations. Nat. Commun., 11.","DOI":"10.1038\/s41467-020-14404-y"},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fchem.2016.00038","article-title":"Metal cations in G-quadruplex folding and stability","volume":"4","author":"Bhattacharyya","year":"2016","journal-title":"Front. Chem."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"4618","DOI":"10.1093\/nar\/gkf597","article-title":"Human telomeric DNA: G-quadruplex, i-motif and Watson-Crick double helix","volume":"30","author":"Phan","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1093\/nar\/gni134","article-title":"Thermal difference spectra: A specific signature for nucleic acid structures","volume":"33","author":"Mergny","year":"2005","journal-title":"Nucleic Acids Res."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.cell.2020.10.028","article-title":"Genome-Wide CRISPR screens reveal host factors critical for SARS-CoV-2 infection","volume":"184","author":"Wei","year":"2020","journal-title":"Cell"},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"707","DOI":"10.1002\/iub.379","article-title":"CNBP: A multifunctional nucleic acid chaperone involved in cell death and proliferation control","volume":"62","author":"Calcaterra","year":"2010","journal-title":"IUBMB Life"},{"key":"ref_64","doi-asserted-by":"crossref","unstructured":"Armas, P., Margarit, E., Mouguelar, V.S., Allende, M.L., and Calcaterra, N.B. (2013). Beyond the binding site: In vivo identification of tbx2, smarca5 and wnt5b as molecular targets of CNBP during embryonic development. PLoS ONE, 8.","DOI":"10.1371\/journal.pone.0063234"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2979","DOI":"10.1016\/j.celrep.2017.02.080","article-title":"The human CCHC-type zinc finger nucleic acid-binding protein binds g-rich elements in target mRNA coding sequences and promotes translation","volume":"18","author":"Benhalevy","year":"2017","journal-title":"Cell Rep."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"David, A.P., Pipier, A., Pascutti, F., Binolfi, A., Weiner, A.M.J., Challier, E., Heckel, S., Calsou, P., Gomez, D., and Calcaterra, N.B. (2019). CNBP controls transcription by unfolding DNA G-quadruplex structures. Nucleic Acids Res., 47.","DOI":"10.1093\/nar\/gkz527"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"3280","DOI":"10.1093\/nar\/gkx071","article-title":"CNBP acts as a key transcriptional regulator of sustained expression of interleukin-6","volume":"45","author":"Lee","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"3136","DOI":"10.1084\/jem.20181031","article-title":"CNBP controls IL-12 gene transcription and Th1 immunity","volume":"215","author":"Chen","year":"2018","journal-title":"J. Exp. Med."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"e1000428","DOI":"10.1371\/journal.ppat.1000428","article-title":"The SARS-Unique Domain (SUD) of SARS coronavirus contains two macrodomains that bind G-quadruplexes","volume":"5","author":"Tan","year":"2009","journal-title":"PLoS Pathog."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"5522","DOI":"10.1002\/anie.201300058","article-title":"Suppression of gene expression by G-quadruplexes in open reading frames depends on G-quadruplex stability","volume":"52","author":"Endoh","year":"2013","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"e1501535","DOI":"10.1126\/sciadv.1501535","article-title":"A highly conserved G-rich consensus sequence in hepatitis C virus core gene represents a new anti\u2013hepatitis C target","volume":"2","author":"Wang","year":"2016","journal-title":"Sci. Adv."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"655","DOI":"10.1038\/nmeth.1362","article-title":"Isolation of deletion alleles by G4 DNA-induced mutagenesis","volume":"6","author":"Pontier","year":"2009","journal-title":"Nat. Methods"},{"key":"ref_73","doi-asserted-by":"crossref","unstructured":"Tateishi-Karimata, H., Isono, N., and Sugimoto, N. (2014). New insights into transcription fidelity: Thermal stability of non-canonical structures in template DNA regulates transcriptional arrest, pause, and slippage. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0090580"},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2350","DOI":"10.1016\/j.bmcl.2010.01.158","article-title":"A reverse transcriptase stop assay revealed diverse quadruplex formations in UTRs in mRNA","volume":"20","author":"Hagihara","year":"2010","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"8120","DOI":"10.1038\/s41598-018-26582-3","article-title":"RNA synthesis is modulated by G-quadruplex formation in Hepatitis C virus negative RNA strand","volume":"8","author":"Jaubert","year":"2018","journal-title":"Sci. Rep."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"1528","DOI":"10.1021\/bi301365g","article-title":"The G-quadruplex augments translation in the 5\u2019 untranslated region of transforming growth factor \u03b22","volume":"52","author":"Agarwala","year":"2013","journal-title":"Biochemistry"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1016\/j.virol.2015.06.016","article-title":"A G-quadruplex-binding macrodomain within the \u201cSARS-unique domain\u201d is essential for the activity of the SARS-coronavirus replication-transcription complex","volume":"484","author":"Kusov","year":"2015","journal-title":"Virology"},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"5661","DOI":"10.1021\/acs.jpclett.0c01097","article-title":"Role of RNA guanine quadruplexes in favoring the dimerization of SARS unique domain in coronaviruses","volume":"11","author":"Hognon","year":"2020","journal-title":"J. Phys. Chem. Lett."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"112494","DOI":"10.1016\/j.bios.2020.112494","article-title":"G-quadruplex based biosensor: A potential tool for SARS-CoV-2 detection","volume":"167","author":"Xi","year":"2020","journal-title":"Biosens. Bioelectron."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1007\/s00705-009-0323-y","article-title":"Interaction between SARS-CoV helicase and a multifunctional cellular protein (Ddx5) revealed by yeast and mammalian cell two-hybrid systems","volume":"154","author":"Chen","year":"2009","journal-title":"Arch. Virol."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"D10","DOI":"10.1093\/nar\/gkaa892","article-title":"Database resources of the national center for biotechnology information","volume":"49","author":"Sayers","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_82","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_83","doi-asserted-by":"crossref","first-page":"170","DOI":"10.1002\/jcc.21596","article-title":"NUPACK: Analysis and design of nucleic acid systems","volume":"32","author":"Zadeh","year":"2011","journal-title":"J. Comput. Chem."},{"key":"ref_84","first-page":"17.8.1","article-title":"Characterization of quadruplex DNA structure by circular dichroism","volume":"68","author":"Gray","year":"2017","journal-title":"Curr. Protoc. Nucleic Acid Chem."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"7171","DOI":"10.1002\/anie.201709184","article-title":"G-Quadruplex secondary structure obtained from circular dichroism spectroscopy","volume":"57","author":"Trent","year":"2018","journal-title":"Angew. Chem. Int. Ed."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"75","DOI":"10.1002\/bip.20189","article-title":"Biophysical properties of quadruple helices of modified human telomeric DNA","volume":"77","author":"Petraccone","year":"2005","journal-title":"Biopolymers"},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"2527","DOI":"10.1038\/nprot.2006.204","article-title":"Using circular dichroism collected as a function of temperature to determine the thermodynamics of protein unfolding and binding interactions","volume":"1","author":"Greenfield","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1006\/jmra.1995.1047","article-title":"Water suppression that works. Excitation sculpting using arbitrary wave-forms and pulsed-field gradients","volume":"112","author":"Hwang","year":"1995","journal-title":"J. Magn. Reson. Ser. A"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"4163","DOI":"10.1093\/nar\/gkw011","article-title":"G-Quadruplexes as novel cis-elements controlling transcription during embryonic development","volume":"44","author":"David","year":"2016","journal-title":"Nucleic Acids Res."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"218","DOI":"10.1038\/nchembio864","article-title":"An RNA G-quadruplex in the 5\u2019 UTR of the NRAS proto-oncogene modulates translation","volume":"3","author":"Kumari","year":"2007","journal-title":"Nat. Chem. Biol."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.pep.2013.10.006","article-title":"Novel high-performance purification protocol of recombinant CNBP suitable for biochemical and biophysical characterization","volume":"93","author":"Challier","year":"2014","journal-title":"Protein Expr. Purif."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"1013","DOI":"10.1002\/jcb.21474","article-title":"Cellular nucleic acid binding protein binds G-rich single-stranded nucleic acids and may function as a nucleic acid chaperone","volume":"103","author":"Armas","year":"2008","journal-title":"J. Cell. Biochem."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1006\/abio.1998.3067","article-title":"Characterization of SYBR gold nucleic acid gel stain: A dye optimized for use with 300-nm ultraviolet transilluminators","volume":"288","author":"Tuma","year":"1999","journal-title":"Anal. Biochem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/5\/2614\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T05:33:20Z","timestamp":1760160800000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/22\/5\/2614"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2021,3,5]]},"references-count":93,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2021,3]]}},"alternative-id":["ijms22052614"],"URL":"https:\/\/doi.org\/10.3390\/ijms22052614","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2021,3,5]]}}}