{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T17:58:11Z","timestamp":1791655091032,"version":"4.3.4"},"reference-count":59,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T00:00:00Z","timestamp":1741910400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["1U19AI171443-01"],"award-info":[{"award-number":["1U19AI171443-01"]}]},{"name":"SPP-ARC (Striving for Pandemic Preparedness\u2014The Alberta Research Consortium)","award":["1U19AI171443-01"],"award-info":[{"award-number":["1U19AI171443-01"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>The Bunyavirales order includes a range of zoonotic viruses, which can cause severe disease in humans. The viral replication machinery is a logical target for the development of direct-acting antivirals. Inhibition of the cap-snatching endonuclease activity of related influenza viruses provides a proof of concept. Using the influenza B virus (IBV) RNA-dependent RNA polymerase complex as a benchmark, we conducted a comparative analysis of endonuclease activities of recombinant full-length bunyaviral L proteins using gel-based assays. The IBV complex demonstrates specific endonucleolytic cleavage and a clear preference for capped substrates. In contrast, severe fever with thrombocytopenia syndrome, Sin Nombre, and Hantaan virus L proteins readily cleave capped and uncapped RNAs to a broader spectrum of RNA fragments. Active site mutants further help to control for the potential of contaminating nucleases, exonuclease activity, and RNA hydrolysis. The influenza cap-snatching inhibitor baloxavir and derivatives have been used to validate this approach. In conclusion, the results of this study demonstrate the importance of assays with single nucleotide resolution and the use of full-length L proteins as a valuable experimental tool to identify selective endonuclease inhibitors.<\/jats:p>","DOI":"10.3390\/v17030420","type":"journal-article","created":{"date-parts":[[2025,3,14]],"date-time":"2025-03-14T08:46:46Z","timestamp":1741942006000},"page":"420","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":6,"title":["Bunyaviral Cap-Snatching Endonuclease Activity and Inhibition with Baloxavir-like Inhibitors in the Context of Full-Length L Proteins"],"prefix":"10.3390","volume":"17","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-5208-6534","authenticated-orcid":false,"given":"Arlo J.","family":"Loutan","sequence":"first","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2E1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baiuyan","family":"Yang","sequence":"additional","affiliation":[{"name":"Calibr-Skaggs Institute for Innovation Medicines at Scripps Research, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Gabrielle","family":"Connolly","sequence":"additional","affiliation":[{"name":"Calibr-Skaggs Institute for Innovation Medicines at Scripps Research, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adam","family":"Montoya","sequence":"additional","affiliation":[{"name":"Calibr-Skaggs Institute for Innovation Medicines at Scripps Research, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Robert J.","family":"Smiley","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2E1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arnab K.","family":"Chatterjee","sequence":"additional","affiliation":[{"name":"Calibr-Skaggs Institute for Innovation Medicines at Scripps Research, La Jolla, CA 92037, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthias","family":"G\u00f6tte","sequence":"additional","affiliation":[{"name":"Department of Medical Microbiology and Immunology, Faculty of Medicine and Dentistry, University of Alberta, Edmonton, AB T6G 2E1, Canada"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,3,14]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"1949","DOI":"10.1007\/s00705-019-04253-6","article-title":"Taxonomy of the order Bunyavirales: Update 2019","volume":"164","author":"Abudurexiti","year":"2019","journal-title":"Arch. Virol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"16","DOI":"10.1177\/00333549101250S305","article-title":"Influenza: The once and future pandemic","volume":"125","author":"Taubenberger","year":"2010","journal-title":"Public Health Rep."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1111\/irv.12570","article-title":"65 years of influenza surveillance by a World Health Organization-coordinated global network","volume":"12","author":"Ziegler","year":"2018","journal-title":"Influenza Other Respir. Viruses"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"779","DOI":"10.1038\/s41467-019-08617-z","article-title":"Non-lytic clearance of influenza B virus from infected cells preserves epithelial barrier function","volume":"10","author":"Dumm","year":"2019","journal-title":"Nat. Commun."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"524","DOI":"10.1016\/j.ijbiomac.2021.01.076","article-title":"Trends and strategies to combat viral infections: A review on FDA approved antiviral drugs","volume":"172","author":"Tompa","year":"2021","journal-title":"Int. J. Biol. Macromol."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"293","DOI":"10.1016\/j.tim.2019.12.006","article-title":"The Cap-Snatching Mechanism of Bunyaviruses","volume":"28","author":"Olschewski","year":"2020","journal-title":"Trends Microbiol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"877","DOI":"10.1016\/j.cell.2020.03.061","article-title":"A Structure-Based Model for the Complete Transcription Cycle of Influenza Polymerase","volume":"181","author":"Wandzik","year":"2020","journal-title":"Cell"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"914","DOI":"10.1038\/nature07745","article-title":"The cap-snatching endonuclease of influenza virus polymerase resides in the PA subunit","volume":"458","author":"Dias","year":"2009","journal-title":"Nature"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"361","DOI":"10.1038\/nature14009","article-title":"Structural insight into cap-snatching and RNA synthesis by influenza polymerase","volume":"516","author":"Reich","year":"2014","journal-title":"Nature"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"118","DOI":"10.1016\/j.virusres.2017.01.018","article-title":"Transcription and replication mechanisms of Bunyaviridae and Arenaviridae L proteins","volume":"234","author":"Ferron","year":"2017","journal-title":"Virus Res."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1934","DOI":"10.1128\/JVI.01657-09","article-title":"An N-terminal region of Lassa virus L protein plays a critical role in transcription but not replication of the virus genome","volume":"84","author":"Lelke","year":"2010","journal-title":"J. Virol."},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Reguera, J., Gerlach, P., Rosenthal, M., Gaudon, S., Coscia, F., G\u00fcnther, S., and Cusack, S. (2016). Comparative Structural and Functional Analysis of Bunyavirus and Arenavirus Cap-Snatching Endonucleases. PLoS Pathog., 12.","DOI":"10.1371\/journal.ppat.1005636"},{"key":"ref_13","doi-asserted-by":"crossref","unstructured":"Gogrefe, N., Reindl, S., G\u00fcnther, S., and Rosenthal, M. (2019). Structure of a functional cap-binding domain in Rift Valley fever virus L protein. PLoS Pathog., 15.","DOI":"10.2210\/pdb6qhg\/pdb"},{"key":"ref_14","doi-asserted-by":"crossref","unstructured":"Meier, K., Thorkelsson, S.R., Durieux Trouilleton, Q., Vogel, D., Yu, D., Kosinski, J., Cusack, S., Malet, H., Gr\u00fcnewald, K., and Quemin, E.R.J. (2023). Structural and functional characterization of the Sin Nombre virus L protein. PLoS Pathog., 19.","DOI":"10.1371\/journal.ppat.1011533"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"5749","DOI":"10.1093\/nar\/gkaa253","article-title":"Structural and functional characterization of the severe fever with thrombocytopenia syndrome virus L protein","volume":"48","author":"Vogel","year":"2020","journal-title":"Nucleic Acids Res."},{"key":"ref_16","doi-asserted-by":"crossref","unstructured":"Reguera, J., Weber, F., and Cusack, S. (2010). Bunyaviridae RNA polymerases (L-protein) have an N-terminal, influenza-like endonuclease domain, essential for viral cap-dependent transcription. PLoS Pathog., 6.","DOI":"10.1371\/journal.ppat.1001101"},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1017\/S0033583510000181","article-title":"Nucleases: Diversity of structure, function and mechanism","volume":"44","author":"Yang","year":"2011","journal-title":"Q. Rev. Biophys."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"e0208521","DOI":"10.1128\/jvi.02085-21","article-title":"Insights into Two-Metal-Ion Catalytic Mechanism of Cap-Snatching Endonuclease of Ebinur Lake Virus in Bunyavirales","volume":"96","author":"Kuang","year":"2022","journal-title":"J. Virol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"109","DOI":"10.1016\/j.antiviral.2018.10.008","article-title":"In vitro characterization of baloxavir acid, a first-in-class cap-dependent endonuclease inhibitor of the influenza virus polymerase PA subunit","volume":"160","author":"Noshi","year":"2018","journal-title":"Antivir. Res."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"913","DOI":"10.1056\/NEJMoa1716197","article-title":"Baloxavir Marboxil for Uncomplicated Influenza in Adults and Adolescents","volume":"379","author":"Sugaya","year":"2018","journal-title":"N. Engl. J. Med."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"309","DOI":"10.1056\/NEJMoa1915341","article-title":"Baloxavir Marboxil for Prophylaxis against Influenza in Household Contacts","volume":"383","author":"Ikematsu","year":"2020","journal-title":"N. Engl. J. Med."},{"key":"ref_22","unstructured":"U.S. Food and Drug Administration (2018). FDA Approves New Drug to Treat Influenza, U.S. Food and Drug Administration."},{"key":"ref_23","doi-asserted-by":"crossref","unstructured":"Omoto, S., Speranzini, V., Hashimoto, T., Noshi, T., Yamaguchi, H., Kawai, M., Kawaguchi, K., Uehara, T., Shishido, T., and Naito, A. (2018). Characterization of influenza virus variants induced by treatment with the endonuclease inhibitor baloxavir marboxil. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-27890-4"},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Todd, B., Tchesnokov, E.P., and G\u00f6tte, M. (2021). The active form of the influenza cap-snatching endonuclease inhibitor baloxavir marboxil is a tight binding inhibitor. J. Biol. Chem., 296.","DOI":"10.1016\/j.jbc.2021.100486"},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"1609","DOI":"10.1093\/nar\/gkaa1294","article-title":"Structural insights into the substrate specificity of the endonuclease activity of the influenza virus cap-snatching mechanism","volume":"49","author":"Kumar","year":"2021","journal-title":"Nucleic Acids Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"374","DOI":"10.1107\/S205225252400304X","article-title":"Biophysical and structural study of La Crosse virus endonuclease inhibition for the development of new antiviral options","volume":"11","author":"Feracci","year":"2024","journal-title":"IUCrJ"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"10914","DOI":"10.1093\/nar\/gkz838","article-title":"Structure and function of the Toscana virus cap-snatching endonuclease","volume":"47","author":"Jones","year":"2019","journal-title":"Nucleic Acids Res."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"e0217321","DOI":"10.1128\/jvi.02173-21","article-title":"Structural and Biochemical Basis for Development of Diketo Acid Inhibitors Targeting the Cap-Snatching Endonuclease of the Ebinur Lake Virus (Order: Bunyavirales)","volume":"96","author":"Kuang","year":"2022","journal-title":"J. Virol."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"e2206104119","DOI":"10.1073\/pnas.2206104119","article-title":"Identification of cap-dependent endonuclease inhibitors with broad-spectrum activity against bunyaviruses","volume":"119","author":"Toba","year":"2022","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_30","doi-asserted-by":"crossref","unstructured":"Taoda, Y., Sato, A., Toba, S., Unoh, Y., Kawai, M., Sasaki, M., Orba, Y., and Sawa, H. (2023). Structure-activity relationship studies of anti-bunyaviral cap-dependent endonuclease inhibitors. Bioorganic Med. Chem. Lett., 83.","DOI":"10.1016\/j.bmcl.2023.129175"},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"19686","DOI":"10.1074\/jbc.RA118.004373","article-title":"Biochemical and structural studies reveal differences and commonalities among cap-snatching endonucleases from segmented negative-strand RNA viruses","volume":"293","author":"Holm","year":"2018","journal-title":"J. Biol. Chem."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"6049","DOI":"10.1093\/nar\/gkae330","article-title":"Structural snapshots of phenuivirus cap-snatching and transcription","volume":"52","author":"Williams","year":"2024","journal-title":"Nucleic Acids Res."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Keown, J.R., Carrique, L., Nilsson-Payant, B.E., Fodor, E., and Grimes, J.M. (2024). Structural characterization of the full-length Hantaan virus polymerase. PLoS Pathog., 20.","DOI":"10.1371\/journal.ppat.1012781"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1583","DOI":"10.1038\/nbt1036","article-title":"Baculovirus expression system for heterologous multiprotein complexes","volume":"22","author":"Berger","year":"2004","journal-title":"Nat. Biotechnol."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"5","DOI":"10.1002\/0471140864.ps0520s51","article-title":"MultiBac: Multigene baculovirus-based eukaryotic protein complex production","volume":"51","author":"Bieniossek","year":"2008","journal-title":"Curr. Protoc. Protein Sci."},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Tchesnokov, E.P., Bailey-Elkin, B.A., Mark, B.L., and G\u00f6tte, M. (2020). Independent inhibition of the polymerase and deubiquitinase activities of the Crimean-Congo Hemorrhagic Fever Virus full-length L-protein. PLoS Neglected Trop. Dis., 14.","DOI":"10.1371\/journal.pntd.0008283"},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Tchesnokov, E.P., Raeisimakiani, P., Ngure, M., Marchant, D., and G\u00f6tte, M. (2018). Recombinant RNA-Dependent RNA Polymerase Complex of Ebola Virus. Sci. Rep., 8.","DOI":"10.1038\/s41598-018-22328-3"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"550","DOI":"10.1038\/nprot.2006.77","article-title":"A detergent-based assay for the detection of promiscuous inhibitors","volume":"1","author":"Feng","year":"2006","journal-title":"Nat. Protoc."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"e05378","DOI":"10.7554\/eLife.05378","article-title":"Unprecedented genomic diversity of RNA viruses in arthropods reveals the ancestry of negative-sense RNA viruses","volume":"4","author":"Li","year":"2015","journal-title":"eLife"},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"3059","DOI":"10.1093\/nar\/gkf436","article-title":"MAFFT: A novel method for rapid multiple sequence alignment based on fast Fourier transform","volume":"30","author":"Katoh","year":"2002","journal-title":"Nucleic Acids Res."},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"1972","DOI":"10.1093\/bioinformatics\/btp348","article-title":"trimAl: A tool for automated alignment trimming in large-scale phylogenetic analyses","volume":"25","year":"2009","journal-title":"Bioinformatics"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1093\/sysbio\/syq010","article-title":"New Algorithms and Methods to Estimate Maximum-Likelihood Phylogenies: Assessing the Performance of PhyML 3.0","volume":"59","author":"Guindon","year":"2010","journal-title":"Syst. Biol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"127","DOI":"10.1093\/bioinformatics\/btl529","article-title":"Interactive Tree Of Life (iTOL): An online tool for phylogenetic tree display and annotation","volume":"23","author":"Letunic","year":"2007","journal-title":"Bioinformatics"},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"2954","DOI":"10.1038\/s41467-023-38555-w","article-title":"Structures of active Hantaan virus polymerase uncover the mechanisms of Hantaviridae genome replication","volume":"14","author":"Arragain","year":"2023","journal-title":"Nat. Commun."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"7018","DOI":"10.1038\/s41467-021-27305-5","article-title":"Conformational changes in Lassa virus L protein associated with promoter binding and RNA synthesis activity","volume":"12","author":"Kouba","year":"2021","journal-title":"Nat. Commun."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"123","DOI":"10.1134\/S002689331101002X","article-title":"Baculovirus expression systems for production of recombinant proteins in insect and mammalian cells","volume":"45","author":"Beljelarskaya","year":"2011","journal-title":"Mol. Biol."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"8088","DOI":"10.1074\/jbc.RA118.006973","article-title":"Biochemical characterization of the Lassa virus L protein","volume":"294","author":"Vogel","year":"2019","journal-title":"J. Biol. Chem."},{"key":"ref_48","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_49","doi-asserted-by":"crossref","first-page":"925","DOI":"10.1016\/j.molcel.2014.12.031","article-title":"Cryo-EM structure of influenza virus RNA polymerase complex at 4.3 \u00c5 resolution","volume":"57","author":"Chang","year":"2015","journal-title":"Mol. Cell"},{"key":"ref_50","first-page":"3353","article-title":"An in vitro fluorescence based study of initiation of RNA synthesis by influenza B polymerase","volume":"45","author":"Reich","year":"2017","journal-title":"Nucleic Acids Res."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"287","DOI":"10.1038\/s41586-019-1530-7","article-title":"Structures of influenza A virus RNA polymerase offer insight into viral genome replication","volume":"573","author":"Fan","year":"2019","journal-title":"Nature"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"460","DOI":"10.1038\/s41594-019-0232-z","article-title":"Structural snapshots of actively transcribing influenza polymerase","volume":"26","author":"Kouba","year":"2019","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"921","DOI":"10.1038\/s41564-021-00916-w","article-title":"Cryo-EM structures of Lassa and Machupo virus polymerases complexed with cognate regulatory Z proteins identify targets for antivirals","volume":"6","author":"Xu","year":"2021","journal-title":"Nat. Microbiol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1093\/nar\/gkac1249","article-title":"Structural insights into viral genome replication by the severe fever with thrombocytopenia syndrome virus L protein","volume":"51","author":"Williams","year":"2023","journal-title":"Nucleic Acids Res."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"4620","DOI":"10.1038\/s41467-024-48848-3","article-title":"Cryo-EM structures of Thogoto virus polymerase reveal unique RNA transcription and replication mechanisms among orthomyxoviruses","volume":"15","author":"Xue","year":"2024","journal-title":"Nat. Commun."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"1183","DOI":"10.1038\/s41594-023-01043-2","article-title":"An intermediate state allows influenza polymerase to switch smoothly between transcription and replication cycles","volume":"30","author":"Li","year":"2023","journal-title":"Nat. Struct. Mol. Biol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"8289","DOI":"10.1093\/nar\/gkt603","article-title":"Characterization of PA-N terminal domain of Influenza A polymerase reveals sequence specific RNA cleavage","volume":"41","author":"Datta","year":"2013","journal-title":"Nucleic Acids Res."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"5754","DOI":"10.1128\/jvi.69.9.5754-5762.1995","article-title":"The 5\u2032 ends of Hantaan virus (Bunyaviridae) RNAs suggest a prime-and-realign mechanism for the initiation of RNA synthesis","volume":"69","author":"Garcin","year":"1995","journal-title":"J. Virol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"6975","DOI":"10.1128\/JVI.00043-13","article-title":"The N Terminus of Andes Virus L Protein Suppresses mRNA and Protein Expression in Mammalian Cells","volume":"87","author":"Heinemann","year":"2013","journal-title":"J. Virol."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/3\/420\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:53:48Z","timestamp":1760028828000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/17\/3\/420"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,3,14]]},"references-count":59,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["v17030420"],"URL":"https:\/\/doi.org\/10.3390\/v17030420","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,3,14]]}}}