{"id":"https://openalex.org/W7225426877","doi":"https://doi.org/10.64898/2026.11.04.764270","title":"RNA-targeted aminopyridine compounds provide a new antifungal strategy","display_name":"RNA-targeted aminopyridine compounds provide a new antifungal strategy","publication_year":2026,"publication_date":"2026-11-06","ids":{"openalex":"https://openalex.org/W7225426877","doi":"https://doi.org/10.64898/2026.11.04.764270"},"language":"en","primary_location":{"id":"doi:10.64898/2026.11.04.764270","doi":"https://doi.org/10.64898/2026.11.04.764270","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.11.04.764270","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/11/06/2026.11.04.764270.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.biorxiv.org/content/biorxiv/early/2026/11/06/2026.11.04.764270.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5016177910","display_name":"Jimin Hwang","orcid":"https://orcid.org/0000-0002-2932-4653","observed_orcids":["https://orcid.org/0000-0002-2932-4653","https://orcid.org/0000-0003-3578-9489"]},"institutions":[{"id":"https://openalex.org/I32971472","display_name":"Yale University","ror":"https://ror.org/03v76x132","country_code":"US","type":"education","lineage":["https://openalex.org/I32971472"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Jimin Hwang","raw_affiliation_strings":["Yale University;"],"raw_orcid":"https://orcid.org/0000-0003-3578-9489","affiliations":[{"raw_affiliation_string":"Yale University;","institution_ids":["https://openalex.org/I32971472"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5057738759","display_name":"Luke J. Sisto","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I32971472","display_name":"Yale University","ror":"https://ror.org/03v76x132","country_code":"US","type":"education","lineage":["https://openalex.org/I32971472"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Luke J Sisto","raw_affiliation_strings":["Yale University;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Yale University;","institution_ids":["https://openalex.org/I32971472"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5095024201","display_name":"Tao Shi","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I32971472","display_name":"Yale University","ror":"https://ror.org/03v76x132","country_code":"US","type":"education","lineage":["https://openalex.org/I32971472"]}],"countries":["US"],"is_corresponding":false,"raw_author_name":"Tao Shi","raw_affiliation_strings":["Yale University;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Yale University;","institution_ids":["https://openalex.org/I32971472"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5069112390","display_name":"Michael C. Van Zandt","orcid":"https://orcid.org/0000-0002-9624-5699","observed_orcids":["https://orcid.org/0000-0002-9624-5699"]},"institutions":[],"countries":[],"is_corresponding":false,"raw_author_name":"Michael C Van Zandt","raw_affiliation_strings":["New England Discovery Partners"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"New England Discovery Partners","institution_ids":[]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5007909912","display_name":"Anna Marie Pyle","orcid":"https://orcid.org/0000-0001-9045-8872","observed_orcids":["https://orcid.org/0000-0001-9045-8872"]},"institutions":[{"id":"https://openalex.org/I32971472","display_name":"Yale University","ror":"https://ror.org/03v76x132","country_code":"US","type":"education","lineage":["https://openalex.org/I32971472"]}],"countries":["US"],"is_corresponding":true,"raw_author_name":"Anna Marie Pyle","raw_affiliation_strings":["Yale University;"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Yale University;","institution_ids":["https://openalex.org/I32971472"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5007909912"],"corresponding_institution_ids":["https://openalex.org/I32971472"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":0,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10521","display_name":"RNA and protein synthesis mechanisms","score":0.6880000233650208,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},"topics":[{"id":"https://openalex.org/T10521","display_name":"RNA and protein synthesis mechanisms","score":0.6880000233650208,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10725","display_name":"RNA Interference and Gene Delivery","score":0.07930000126361847,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T10432","display_name":"DNA and Nucleic Acid Chemistry","score":0.06400000303983688,"subfield":{"id":"https://openalex.org/subfields/1312","display_name":"Molecular Biology"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/group-i-introns","display_name":"group I introns","score":0.8989999890327454},{"id":"https://openalex.org/keywords/self-splicing-ribozymes","display_name":"self-splicing ribozymes","score":0.9369999766349792},{"id":"https://openalex.org/keywords/candida-albicans","display_name":"Candida albicans","score":0.949999988079071},{"id":"https://openalex.org/keywords/structure-activity-relationship","display_name":"structure-activity relationship","score":0.9089999794960022},{"id":"https://openalex.org/keywords/diamine-ligands","display_name":"diamine ligands","score":0.6269999742507935},{"id":"https://openalex.org/keywords/amphotericin-b-synergy","display_name":"amphotericin B synergy","score":0.8389999866485596},{"id":"https://openalex.org/keywords/combination-antifungal-therapy","display_name":"combination antifungal therapy","score":0.7590000033378601},{"id":"https://openalex.org/keywords/target-engagement","display_name":"target engagement","score":0.6449999809265137},{"id":"https://openalex.org/keywords/rna-targeted-drug-discovery","display_name":"RNA-targeted drug discovery","score":0.6510000228881836}],"concepts":[{"id":"https://openalex.org/C185592680","wikidata":"https://www.wikidata.org/wiki/Q2329","display_name":"Chemistry","level":0,"score":0.5579000115394592},{"id":"https://openalex.org/C2778087735","wikidata":"https://www.wikidata.org/wiki/Q2393470","display_name":"2-Aminopyridine","level":2,"score":0.5408999919891357},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.5354999899864197},{"id":"https://openalex.org/C2780917455","wikidata":"https://www.wikidata.org/wiki/Q310443","display_name":"Candida albicans","level":2,"score":0.519599974155426},{"id":"https://openalex.org/C194051981","wikidata":"https://www.wikidata.org/wiki/Q1337691","display_name":"Economic shortage","level":3,"score":0.5026000142097473},{"id":"https://openalex.org/C2779629538","wikidata":"https://www.wikidata.org/wiki/Q412223","display_name":"Amphotericin B","level":3,"score":0.47909998893737793},{"id":"https://openalex.org/C67705224","wikidata":"https://www.wikidata.org/wiki/Q11053","display_name":"RNA","level":3,"score":0.4659000039100647},{"id":"https://openalex.org/C116569031","wikidata":"https://www.wikidata.org/wiki/Q899107","display_name":"Ligand (biochemistry)","level":3,"score":0.45969998836517334},{"id":"https://openalex.org/C2779548794","wikidata":"https://www.wikidata.org/wiki/Q578726","display_name":"Antifungal","level":2,"score":0.44339999556541443},{"id":"https://openalex.org/C2779222958","wikidata":"https://www.wikidata.org/wiki/Q45422","display_name":"Yeast","level":2,"score":0.3822000026702881},{"id":"https://openalex.org/C71240020","wikidata":"https://www.wikidata.org/wiki/Q186011","display_name":"Stereochemistry","level":1,"score":0.3447999954223633},{"id":"https://openalex.org/C55493867","wikidata":"https://www.wikidata.org/wiki/Q7094","display_name":"Biochemistry","level":1,"score":0.34310001134872437},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.32899999618530273},{"id":"https://openalex.org/C76346623","wikidata":"https://www.wikidata.org/wiki/Q205858","display_name":"Ribozyme","level":4,"score":0.32510000467300415},{"id":"https://openalex.org/C2778784160","wikidata":"https://www.wikidata.org/wiki/Q419130","display_name":"Peroxynitrite","level":4,"score":0.32510000467300415},{"id":"https://openalex.org/C21951064","wikidata":"https://www.wikidata.org/wiki/Q899212","display_name":"Combinatorial chemistry","level":1,"score":0.3147999942302704},{"id":"https://openalex.org/C89423630","wikidata":"https://www.wikidata.org/wiki/Q7193","display_name":"Microbiology","level":1,"score":0.305400013923645},{"id":"https://openalex.org/C109159458","wikidata":"https://www.wikidata.org/wiki/Q919283","display_name":"Haematopoiesis","level":3,"score":0.27900001406669617}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.11.04.764270","doi":"https://doi.org/10.64898/2026.11.04.764270","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.11.04.764270","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/11/06/2026.11.04.764270.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.64898/2026.11.04.764270","doi":"https://doi.org/10.64898/2026.11.04.764270","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.11.04.764270","pdf_url":"https://www.biorxiv.org/content/biorxiv/early/2026/11/06/2026.11.04.764270.full.pdf","source":{"id":"https://openalex.org/S4306402567","display_name":"bioRxiv (Cold Spring Harbor Laboratory)","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":false,"listed_in":[],"host_organization":"https://openalex.org/I2750212522","host_organization_name":"Cold Spring Harbor Laboratory","host_organization_lineage":["https://openalex.org/I2750212522"],"host_organization_lineage_names":[],"type":"repository"},"license":"cc-by","license_id":"https://openalex.org/licenses/cc-by","version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"bioRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"score":0.8048999905586243,"id":"https://metadata.un.org/sdg/3","display_name":"Good health and well-being"}],"study_designs":[],"awards":[],"funders":[{"id":"https://openalex.org/F4320306082","display_name":"Howard Hughes Medical Institute","ror":"https://ror.org/006w34k90"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7225426877.pdf","grobid_xml":"https://content.openalex.org/works/W7225426877.grobid-xml"},"referenced_works_count":37,"referenced_works":["https://openalex.org/W1602695373","https://openalex.org/W1931081986","https://openalex.org/W1985368446","https://openalex.org/W1988744922","https://openalex.org/W1989872688","https://openalex.org/W2058276221","https://openalex.org/W2080251448","https://openalex.org/W2092915328","https://openalex.org/W2097971843","https://openalex.org/W2105292164","https://openalex.org/W2105957252","https://openalex.org/W2128551987","https://openalex.org/W2168154114","https://openalex.org/W2169751581","https://openalex.org/W2346094579","https://openalex.org/W2747225324","https://openalex.org/W2810410733","https://openalex.org/W2820941669","https://openalex.org/W2883929619","https://openalex.org/W2888364023","https://openalex.org/W2895994095","https://openalex.org/W2909620196","https://openalex.org/W2935525534","https://openalex.org/W2949078846","https://openalex.org/W3123805313","https://openalex.org/W3160838913","https://openalex.org/W4220972968","https://openalex.org/W4224245533","https://openalex.org/W4280571115","https://openalex.org/W4290672950","https://openalex.org/W4319296069","https://openalex.org/W4321615987","https://openalex.org/W4391257042","https://openalex.org/W4392764881","https://openalex.org/W4410203159","https://openalex.org/W4413807002","https://openalex.org/W4415717489"],"related_works":["https://openalex.org/W2895994095","https://openalex.org/W4406517986","https://openalex.org/W4378983234","https://openalex.org/W2070879114","https://openalex.org/W4410203159","https://openalex.org/W2186781913","https://openalex.org/W2077322758","https://openalex.org/W7133531616","https://openalex.org/W4386020091","https://openalex.org/W3127752074"],"abstract_inverted_index":{"While":[0],"RNA":[1,98],"is":[2,9,21],"an":[3,61,70],"emerging":[4],"therapeutic":[5],"target":[6,126,144],"class,":[7],"progress":[8],"limited":[10],"by":[11],"a":[12,30,43,55,84,92,118,139,146],"shortage":[13],"of":[14,50],"well-defined":[15],"targets":[16],"in":[17,34,128],"which":[18],"ligand":[19],"binding":[20],"coupled":[22],"to":[23,64],"measurable":[24],"function.":[25],"The":[26],"group":[27,135],"I":[28,136],"intron,":[29],"self-splicing":[31],"ribozyme":[32],"essential":[33],"fungal":[35,134],"mitochondria":[36],"but":[37],"absent":[38],"from":[39],"humans,":[40],"offers":[41],"both":[42],"tractable":[44],"platform":[45,148],"for":[46,95,120,149],"exploring":[47],"first":[48],"principles":[49],"small":[51],"molecule-RNA":[52],"targeting":[53],"and":[54,68,100,145],"selective":[56],"antifungal":[57,143],"target.":[58],"We":[59],"recalibrated":[60],"intron-splicing":[62],"assay":[63],"approximate":[65],"cellular":[66],"conditions":[67],"performed":[69],"extensive,":[71],"cryo-EM-guided":[72],"structure-activity":[73],"relationship":[74],"campaign":[75],"against":[76,114],"the":[77,133],"Candida":[78],"albicans":[79],"mtLSU":[80],"intron.":[81],"Ligands":[82],"containing":[83],"flexible":[85],"diamine":[86],"outperformed":[87],"conformationally":[88],"constrained":[89],"analogues,":[90],"suggesting":[91,117],"general":[93],"principle":[94],"engaging":[96],"dynamic":[97],"surfaces":[99],"yielding":[101],"lead":[102],"aminopyridine":[103],"56":[104,109],"(IC\u2085\u2080":[105],"21.6":[106],"nM).":[107],"Compound":[108],"synergizes":[110],"with":[111],"amphotericin":[112],"B":[113],"C.":[115],"albicans,":[116],"path":[119],"combination":[121],"therapies.":[122],"RT-qPCR":[123],"confirmed":[124],"direct":[125],"engagement":[127],"cells.":[129],"This":[130],"work":[131],"establishes":[132],"intron":[137],"as":[138],"viable,":[140],"mechanistically":[141],"distinct":[142],"model":[147],"RNA-targeted":[150],"discovery.":[151]},"counts_by_year":[],"updated_date":"2026-11-09T13:22:03.289127","created_date":"2026-11-07T00:00:00"}