{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,8]],"date-time":"2026-06-08T13:10:11Z","timestamp":1780924211744,"version":"3.54.1"},"reference-count":51,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2024,12,23]],"date-time":"2024-12-23T00:00:00Z","timestamp":1734912000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["chemistry-europe.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["Chemistry A European J"],"published-print":{"date-parts":[[2025,1,17]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>The development of antiviral drugs against the Severe Acute Respiratory Syndrome coronavirus 2 (SARS\u2010CoV\u20102) responsible for the recent Covid\u201019 pandemic is crucial, as treatment options remain limited and vaccination does not prevent (re)infection. Two relatively underexplored targets of this virus are the 3\u2032\u20105\u2032 exoribonuclease (ExoN) and the 2\u2019\u2010<jats:italic>O<\/jats:italic>\u2010methyltransferase (2\u2032\u2010<jats:italic>O<\/jats:italic>\u2010MTase), both essential for viral viability. The non\u2010structural proteins Nsp14 and Nsp16 exhibit enzymatic activities for ExoN and 2\u2032\u2010<jats:italic>O<\/jats:italic>\u2010MTase, respectively, especially when in complex with their co\u2010factor protein Nsp10. The study focuses on the use of target\u2010directed dynamic combinatorial chemistry (tdDCC) to identify binders of Nsp10, aiming to disturb the protein\u2010protein interactions (PPI) involving Nsp10\u2010Nsp14, as well as Nsp10\u2010Nsp16. We synthesised the hits and evaluated them to assess Nsp10 affinity, ExoN and 2\u2032\u2010<jats:italic>O<\/jats:italic>\u2010MTase activities inhibition, and antiviral activity in hCoV\u2010229E and SARS\u2010CoV\u20102\u2010infected whole\u2010cell settings. This study reports a novel class of ExoN and\/or 2\u2032\u2010<jats:italic>O<\/jats:italic>\u2010MTase inhibitors exhibiting antiviral activity against coronaviruses.<\/jats:p>","DOI":"10.1002\/chem.202403390","type":"journal-article","created":{"date-parts":[[2024,12,15]],"date-time":"2024-12-15T22:24:03Z","timestamp":1734301443000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Dynamic Combinatorial Chemistry Unveils Nsp10 Inhibitors with Antiviral Potential Against SARS\u2010CoV\u20102"],"prefix":"10.1002","volume":"31","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2674-9605","authenticated-orcid":false,"given":"Ravindra P.","family":"Jumde","sequence":"first","affiliation":[{"name":"Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) \u2013 Helmholtz Centre for Infection Research (HZI)  Campus E 8.1 66123 Saarbr\u00fccken Germany"},{"name":"Current address Global Antibiotic Research &amp; Development Partnership (GARDP)  Chemin Camille-Vidart 15 1202 Geneva Switzerland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8945-8680","authenticated-orcid":false,"given":"Gwena\u00eblle","family":"J\u00e9z\u00e9quel","sequence":"additional","affiliation":[{"name":"Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) \u2013 Helmholtz Centre for Infection Research (HZI)  Campus E 8.1 66123 Saarbr\u00fccken Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0458-1036","authenticated-orcid":false,"given":"Margarida","family":"Saramago","sequence":"additional","affiliation":[{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier Universidade Nova de Lisboa  Avenida da Rep\u00fablica 2780-157 Oeiras Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolas","family":"Frank","sequence":"additional","affiliation":[{"name":"Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) \u2013 Helmholtz Centre for Infection Research (HZI)  Campus E 8.1 66123 Saarbr\u00fccken Germany"},{"name":"Saarland University Department of Pharmacy  Campus E 8.1 66123 Saarbr\u00fccken Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3319-6356","authenticated-orcid":false,"given":"Sebastian","family":"Adam","sequence":"additional","affiliation":[{"name":"Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) \u2013 Helmholtz Centre for Infection Research (HZI)  Campus E 8.1 66123 Saarbr\u00fccken Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0005-3380-5993","authenticated-orcid":false,"given":"Marta V.","family":"Cunha","sequence":"additional","affiliation":[{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier Universidade Nova de Lisboa  Avenida da Rep\u00fablica 2780-157 Oeiras Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3560-7956","authenticated-orcid":false,"given":"Chantal D.","family":"Bader","sequence":"additional","affiliation":[{"name":"Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) \u2013 Helmholtz Centre for Infection Research (HZI)  Campus E 8.1 66123 Saarbr\u00fccken Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2649-7556","authenticated-orcid":false,"given":"Antonia P.","family":"Gunesch","sequence":"additional","affiliation":[{"name":"Institute for Experimental Virology Twincore \u2013 Centre for Experimental and Clinical Infection Research  Feodor-Lynen-Str. 7 30625 Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7502-0431","authenticated-orcid":false,"given":"Natalie M.","family":"K\u00f6hler","sequence":"additional","affiliation":[{"name":"Institute for Experimental Virology Twincore \u2013 Centre for Experimental and Clinical Infection Research  Feodor-Lynen-Str. 7 30625 Hannover Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2306-2071","authenticated-orcid":false,"given":"Sandra","family":"Johannsen","sequence":"additional","affiliation":[{"name":"Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) \u2013 Helmholtz Centre for Infection Research (HZI)  Campus E 8.1 66123 Saarbr\u00fccken Germany"},{"name":"Saarland University Department of Pharmacy  Campus E 8.1 66123 Saarbr\u00fccken Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Spyridon","family":"Bousis","sequence":"additional","affiliation":[{"name":"Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) \u2013 Helmholtz Centre for Infection Research (HZI)  Campus E 8.1 66123 Saarbr\u00fccken Germany"},{"name":"Saarland University Department of Pharmacy  Campus E 8.1 66123 Saarbr\u00fccken Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6789-4422","authenticated-orcid":false,"given":"Thomas","family":"Pietschmann","sequence":"additional","affiliation":[{"name":"Institute for Experimental Virology Twincore \u2013 Centre for Experimental and Clinical Infection Research  Feodor-Lynen-Str. 7 30625 Hannover Germany"},{"name":"Cluster of Excellence RESIST (EXC 2155) Hannover Medical School  30625 Hannover Germany"},{"name":"Helmholtz International Lab for Anti-infectives  Campus E 8.1 66123 Saarbr\u00fccken Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9788-7562","authenticated-orcid":false,"given":"Rute G.","family":"Matos","sequence":"additional","affiliation":[{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier Universidade Nova de Lisboa  Avenida da Rep\u00fablica 2780-157 Oeiras Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1042-5665","authenticated-orcid":false,"given":"Rolf","family":"M\u00fcller","sequence":"additional","affiliation":[{"name":"Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) \u2013 Helmholtz Centre for Infection Research (HZI)  Campus E 8.1 66123 Saarbr\u00fccken Germany"},{"name":"Saarland University Department of Pharmacy  Campus E 8.1 66123 Saarbr\u00fccken Germany"},{"name":"Cluster of Excellence RESIST (EXC 2155) Hannover Medical School  30625 Hannover Germany"},{"name":"Helmholtz International Lab for Anti-infectives  Campus E 8.1 66123 Saarbr\u00fccken Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1934-9301","authenticated-orcid":false,"given":"Cec\u00edlia M.","family":"Arraiano","sequence":"additional","affiliation":[{"name":"Instituto de Tecnologia Qu\u00edmica e Biol\u00f3gica Ant\u00f3nio Xavier Universidade Nova de Lisboa  Avenida da Rep\u00fablica 2780-157 Oeiras Portugal"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8734-4663","authenticated-orcid":false,"given":"Anna K. H.","family":"Hirsch","sequence":"additional","affiliation":[{"name":"Helmholtz Institute for Pharmaceutical Research Saarland (HIPS) \u2013 Helmholtz Centre for Infection Research (HZI)  Campus E 8.1 66123 Saarbr\u00fccken Germany"},{"name":"Saarland University Department of Pharmacy  Campus E 8.1 66123 Saarbr\u00fccken Germany"},{"name":"Cluster of Excellence RESIST (EXC 2155) Hannover Medical School  30625 Hannover Germany"},{"name":"Helmholtz International Lab for Anti-infectives  Campus E 8.1 66123 Saarbr\u00fccken Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2024,12,23]]},"reference":[{"key":"e_1_2_11_1_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa2001017"},{"key":"e_1_2_11_2_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41586-020-2012-7"},{"key":"e_1_2_11_3_1","doi-asserted-by":"publisher","DOI":"10.1093\/cid\/ciab079"},{"key":"e_1_2_11_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s43440-020-00155-6"},{"key":"e_1_2_11_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.abl4784"},{"key":"e_1_2_11_6_1","unstructured":"U.\u2005S. Food and Drug Administration Fact Sheet for Healthcare Providers Emergency Use Authorization (EUA) for Paxlovid US Food & Drug Administration (FDA) 2021 No. 1 1\u201329."},{"key":"e_1_2_11_7_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cell.2020.04.011"},{"key":"e_1_2_11_8_1","doi-asserted-by":"publisher","DOI":"10.3390\/cells10040821"},{"key":"e_1_2_11_9_1","doi-asserted-by":"publisher","DOI":"10.1002\/jmv.27009"},{"key":"e_1_2_11_10_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1003565"},{"key":"e_1_2_11_11_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01246-20"},{"key":"e_1_2_11_12_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1009226"},{"key":"e_1_2_11_13_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.ppat.1000896"},{"key":"e_1_2_11_14_1","doi-asserted-by":"publisher","DOI":"10.1111\/febs.15815"},{"key":"e_1_2_11_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jbc.2021.101518"},{"key":"e_1_2_11_16_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2021.03.024"},{"key":"e_1_2_11_17_1","doi-asserted-by":"publisher","DOI":"10.3390\/diseases9010012"},{"key":"e_1_2_11_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/bs.aivir.2016.08.008"},{"key":"e_1_2_11_19_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.virusres.2014.09.009"},{"key":"e_1_2_11_20_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M114.577353"},{"key":"e_1_2_11_21_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms21197375"},{"key":"e_1_2_11_22_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab320"},{"key":"e_1_2_11_23_1","doi-asserted-by":"publisher","DOI":"10.1126\/scisignal.abe1202"},{"key":"e_1_2_11_24_1","doi-asserted-by":"publisher","DOI":"10.1128\/JVI.01296-07"},{"key":"e_1_2_11_25_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.01503-17"},{"key":"e_1_2_11_26_1","doi-asserted-by":"publisher","DOI":"10.1128\/mBio.00221-18"},{"key":"e_1_2_11_27_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41594-021-00570-0"},{"key":"e_1_2_11_28_1","doi-asserted-by":"publisher","DOI":"10.1042\/BCJ20210199"},{"key":"e_1_2_11_29_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1CB00135C"},{"key":"e_1_2_11_30_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41418-021-00900-1"},{"key":"e_1_2_11_31_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab1303"},{"key":"e_1_2_11_32_1","doi-asserted-by":"publisher","DOI":"10.3390\/ph14121243"},{"key":"e_1_2_11_33_1","doi-asserted-by":"publisher","DOI":"10.1080\/14756366.2021.1885396"},{"key":"e_1_2_11_34_1","doi-asserted-by":"publisher","DOI":"10.1080\/10799893.2020.1772298"},{"key":"e_1_2_11_35_1","doi-asserted-by":"publisher","DOI":"10.1002\/ejoc.201900327"},{"key":"e_1_2_11_36_1","doi-asserted-by":"publisher","DOI":"10.1039\/C4CS00493K"},{"key":"e_1_2_11_37_1","doi-asserted-by":"publisher","DOI":"10.1002\/chem.201803365"},{"key":"e_1_2_11_38_1","doi-asserted-by":"publisher","DOI":"10.1039\/D1SC00330E"},{"key":"e_1_2_11_39_1","doi-asserted-by":"publisher","DOI":"10.1038\/nchem.658"},{"key":"e_1_2_11_40_1","doi-asserted-by":"publisher","DOI":"10.1002\/anie.201202000"},{"key":"e_1_2_11_41_1","doi-asserted-by":"publisher","DOI":"10.1021\/acsmedchemlett.9b00541"},{"key":"e_1_2_11_42_1","doi-asserted-by":"publisher","DOI":"10.1039\/jr9520004735"},{"key":"e_1_2_11_43_1","doi-asserted-by":"publisher","DOI":"10.3389\/fmolb.2022.837901"},{"key":"e_1_2_11_44_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkab320"},{"key":"e_1_2_11_45_1","doi-asserted-by":"publisher","DOI":"10.1086\/377612"},{"key":"e_1_2_11_46_1","first-page":"1","volume":"118","author":"Hsu J. C. C.","year":"2021","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"e_1_2_11_47_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0508200103"},{"key":"e_1_2_11_48_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0032857"},{"key":"e_1_2_11_49_1","doi-asserted-by":"publisher","DOI":"10.1155\/2013\/197475"},{"key":"e_1_2_11_50_1","doi-asserted-by":"publisher","DOI":"10.1039\/C9TB00560A"},{"key":"e_1_2_11_51_1","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/15.21.8783"}],"container-title":["Chemistry \u2013 A European Journal"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/pdf\/10.1002\/chem.202403390","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,12]],"date-time":"2025-10-12T08:56:24Z","timestamp":1760259384000},"score":1,"resource":{"primary":{"URL":"https:\/\/chemistry-europe.onlinelibrary.wiley.com\/doi\/10.1002\/chem.202403390"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2024,12,23]]},"references-count":51,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2025,1,17]]}},"alternative-id":["10.1002\/chem.202403390"],"URL":"https:\/\/doi.org\/10.1002\/chem.202403390","archive":["Portico"],"relation":{},"ISSN":["0947-6539","1521-3765"],"issn-type":[{"value":"0947-6539","type":"print"},{"value":"1521-3765","type":"electronic"}],"subject":[],"published":{"date-parts":[[2024,12,23]]},"assertion":[{"value":"2024-09-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2024-12-23","order":3,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}],"article-number":"e202403390"}}