{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T09:16:40Z","timestamp":1788167800582,"version":"build-2803163510"},"reference-count":26,"publisher":"American Chemical Society (ACS)","issue":"16","license":[{"start":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T00:00:00Z","timestamp":1785974400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100007165","name":"University of Missouri","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100007165","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,8,24]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>The Critical Assessment of Computational Hit-Finding Experiments (CACHE) Challenges came forward as real-world stress tests for virtual screening methods. In Challenge #2, the focus was on SARS-CoV-2 NSP13 helicase\u2500the most conserved protein across Coronaviridae and a prime target for broad-spectrum antivirals. We brought in FRASE-based hit-finding robot (FRASE-bot), our fragment-based screening engine that delimits target-relevant chemical space and identifies likely binding sites. Guided by FRASE-bot, 79 compounds were selected over two rounds. Round 1 delivered four confirmed binders of NSP13 with dissociation constants between 11 and 61 \u03bcM. Round 2 pushed further: five analogs bound in the micromolar range, with compounds 8 and 9 (derived from the parent hit 2) showing clear gains over other CACHE participants. With successful runs in both CACHE #1 and #2, FRASE-bot is proving its ability to tackle tough protein targets. The identification of validated binders targeting the RNA-binding groove of SARS-CoV-2 NSP13 holds significant promise for antiviral drug discovery.<\/jats:p>","DOI":"10.1021\/acs.jcim.6c00560","type":"journal-article","created":{"date-parts":[[2026,8,6]],"date-time":"2026-08-06T18:01:32Z","timestamp":1786039292000},"page":"10318-10325","source":"Crossref","is-referenced-by-count":0,"title":["Targeting the RNA-Binding\nSite of SARS-CoV-2\nNSP13 by FRASE-bot in CACHE Challenge #2"],"prefix":"10.1021","volume":"66","author":[{"given":"Xiaowen","family":"Wang","sequence":"first","affiliation":[{"name":"University of Missouri , , , ,","place":["Columbia, Missouri, United States, 65211"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akhila","family":"Mettu","sequence":"additional","affiliation":[{"name":"University of Missouri , , , ,","place":["Columbia, Missouri, United States, 65211"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Oleksandra","family":"Herasymenko","sequence":"additional","affiliation":[{"name":"University of Toronto , , , ,","place":["Toronto, Ontario, Canada, M5G 1L7"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Madhushika","family":"Silva","sequence":"additional","affiliation":[{"name":"University Health Network , , , ,","place":["Toronto, Ontario, Canada, M5G 2C4"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Scott","family":"Houliston","sequence":"additional","affiliation":[{"name":"University Health Network , , , ,","place":["Toronto, Ontario, Canada, M5G 2C4"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene","family":"Chau","sequence":"additional","affiliation":[{"name":"University of Toronto , , , ,","place":["Toronto, Ontario, Canada, M5G 1L7"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Pegah","family":"Ghiabi","sequence":"additional","affiliation":[{"name":"University of Toronto , , , ,","place":["Toronto, Ontario, Canada, M5G 1L7"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7112-337X","authenticated-orcid":true,"given":"Elisa","family":"Gibson","sequence":"additional","affiliation":[{"name":"University Health Network , , , ,","place":["Toronto, Ontario, Canada, M5G 2C4"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sumera","family":"Perveen","sequence":"additional","affiliation":[{"name":"University of Toronto , , , ,","place":["Toronto, Ontario, Canada, M5G 1L7"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Almagul","family":"Seitova","sequence":"additional","affiliation":[{"name":"University Health Network , , , ,","place":["Toronto, Ontario, Canada, M5G 2C4"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1047-3309","authenticated-orcid":true,"given":"Matthieu","family":"Schapira","sequence":"additional","affiliation":[{"name":"University of Toronto , , , ,","place":["Toronto, Ontario, Canada, M5G 1L7"]},{"name":"University Health Network , , , ,","place":["Toronto, Ontario, Canada, M5G 2C4"]},{"name":"University of Toronto , , , ,","place":["Toronto, Ontario, Canada, M5S 1A8"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8479-8555","authenticated-orcid":true,"given":"Dmitri","family":"Kireev","sequence":"additional","affiliation":[{"name":"University of Missouri , , , ,","place":["Columbia, Missouri, United States, 65211"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2026,8,6]]},"reference":[{"key":"2026083104302002900_cit1","doi-asserted-by":"publisher","first-page":"287","DOI":"10.1038\/s41570-022-00363-z","article-title":"CACHE (Critical Assessment\nof Computational Hit-finding Experiments): A public\u2013private\npartnership benchmarking initiative to enable the development of computational\nmethods for hit-finding","volume":"6","author":"Ackloo","year":"2022","journal-title":"Nat. Rev. Chem."},{"key":"2026083104302002900_cit2","unstructured":"CACHE.\n          \n          Finding Ligands Targeting\nthe Conserved RNA\nBinding Site of SARS-CoV-2 NSP13; 2022. https:\/\/cache-challenge.org\/challenges\/finding-ligands-targeting-the-conserved-rna-binding-site-of-sars-cov-2-nsp13."},{"key":"2026083104302002900_cit3","unstructured":"World Health Organization.\n          \n          COVID-19\ndashboard; 2024. https:\/\/covid19.who.int\/."},{"issue":"1","key":"2026083104302002900_cit4","doi-asserted-by":"publisher","first-page":"1418","DOI":"10.1080\/22221751.2020.1780953","article-title":"SARS-CoV-2 nsp13, nsp14,\nnsp15 and orf6 function\nas potent interferon antagonists","volume":"9","author":"Yuen","year":"2020","journal-title":"Emerging Microbes\nInfect."},{"issue":"1","key":"2026083104302002900_cit5","doi-asserted-by":"publisher","first-page":"4848","DOI":"10.1038\/s41467-021-25166-6","article-title":"Structure, mechanism\nand crystallographic fragment screening of the SARS-CoV-2 NSP13 helicase","volume":"12","author":"Newman","year":"2021","journal-title":"Nat. Commun."},{"issue":"3","key":"2026083104302002900_cit6","doi-asserted-by":"publisher","first-page":"321","DOI":"10.1007\/s12250-020-00242-1","article-title":"SARS-Coronavirus-2 Nsp13 Possesses\nNTPase and RNA Helicase Activities\nThat Can Be Inhibited by Bismuth Salts","volume":"35","author":"Shu","year":"2020","journal-title":"Virol.\nSin."},{"issue":"8","key":"2026083104302002900_cit7","doi-asserted-by":"publisher","first-page":"4212","DOI":"10.1021\/acs.jproteome.1c00206","article-title":"Genetic Variability\nof the SARS-CoV-2 Pocketome","volume":"20","author":"Yazdani","year":"2021","journal-title":"J. Proteome Res."},{"key":"2026083104302002900_cit8","unstructured":"Yazdani, S.; De Maio, N.; Ding, Y.; Goldman, N.; Schapira, M.\n          Druggability and genetic\nvariability of SARS-CoV-2 nsp13; 2020. https:\/\/apps.thesgc.org\/SARSCoV2_pocketome\/icm\/nsp13_html.html."},{"issue":"1","key":"2026083104302002900_cit9","doi-asserted-by":"publisher","first-page":"5564","DOI":"10.1038\/s41467-024-49892-9","article-title":"In silico\nfragment-based discovery of CIB1-directed anti-tumor agents by FRASE-bot","volume":"15","author":"An","year":"2024","journal-title":"Nat. Commun."},{"issue":"39","key":"2026083104302002900_cit10","doi-asserted-by":"publisher","first-page":"15700","DOI":"10.1021\/jacs.9b08660","article-title":"Data-Driven Construction of Antitumor Agents with Controlled\nPolypharmacology","volume":"141","author":"Da","year":"2019","journal-title":"J. Am. Chem. 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Dis."}],"container-title":["Journal of Chemical Information\nand Modeling"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pubs.acs.org\/doi\/pdf\/10.1021\/acs.jcim.6c00560","content-type":"application\/pdf","content-version":"vor","intended-application":"unspecified"},{"URL":"https:\/\/pubs.acs.org\/jcisd8\/article-pdf\/66\/16\/10318\/66449807\/acs.jcim.6c00560.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/pubs.acs.org\/jcisd8\/article-pdf\/66\/16\/10318\/66449807\/acs.jcim.6c00560.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,8,31]],"date-time":"2026-08-31T08:30:32Z","timestamp":1788165032000},"score":1,"resource":{"primary":{"URL":"https:\/\/pubs.acs.org\/jcisd8\/article\/66\/16\/10318\/5249727\/Targeting-the-RNA-Binding-Site-of-SARS-CoV-2-NSP13"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,8,6]]},"references-count":26,"journal-issue":{"issue":"16","published-online":{"date-parts":[[2026,8,6]]},"published-print":{"date-parts":[[2026,8,24]]}},"URL":"https:\/\/doi.org\/10.1021\/acs.jcim.6c00560","relation":{"has-preprint":[{"id-type":"doi","id":"10.26434\/chemrxiv.15000748\/v2","asserted-by":"object"}]},"ISSN":["1549-9596","1549-960X"],"issn-type":[{"value":"1549-9596","type":"print"},{"value":"1549-960X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,8,6]]}}}