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Since their discovery, Adhirons have been isolated against over 350 targets, and they can be used for many research applications. However, their therapeutic application is at present in its early stages, hence the interest in developing novel small molecules to mimic their effect. We develop a pipeline for small molecule discovery where Adhirons act as starting templates in a ligand-based virtual screening workflow. For proof of concept, we use Adhirons against two viral systems: Crimean-Congo Haemorrhagic Fever Virus and Influenza A Virus. In both cases, a hit was identified from the mimics using biophysical and cell-based assays, highlighting how Adhirons, commercial libraries and structural approaches can be combined to accelerate small molecule inhibitor discovery of viruses.<\/jats:p>","DOI":"10.1038\/s42003-025-09137-x","type":"journal-article","created":{"date-parts":[[2025,11,26]],"date-time":"2025-11-26T15:32:27Z","timestamp":1764171147000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Adhirons are efficient tools to guide antiviral ligand discovery"],"prefix":"10.1038","volume":"8","author":[{"given":"Alex J.","family":"Flynn","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2978-2192","authenticated-orcid":false,"given":"Alex","family":"Derry","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8239-2738","authenticated-orcid":false,"given":"Oliver","family":"Debski-Antoniak","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6869-4414","authenticated-orcid":false,"given":"Stephen P.","family":"Muench","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9084-2927","authenticated-orcid":false,"given":"Juan","family":"Fontana","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4846-9097","authenticated-orcid":false,"given":"Katie J.","family":"Simmons","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2025,11,26]]},"reference":[{"key":"9137_CR1","doi-asserted-by":"publisher","first-page":"708","DOI":"10.1038\/s41587-019-0175-2","volume":"37","author":"RF Beall","year":"2019","unstructured":"Beall, R. 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J.F. is an Editorial Board Member for\n                      Communications Biology\n                      , but was not involved in the editorial review of, nor the decision to publish this article.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}],"article-number":"1755"}}