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Despite the availability of antibiotics and antivirals, treatment of concurrent IAV and invasive group A streptococcal infections remains challenging. As bioinformatic drug repurposing represents a cost- and time-effective manner for discovering novel treatments, this study aimed at the identification of novel therapeutic options for the\n                      <jats:italic>S. pyogenes<\/jats:italic>\n                      -IAV coinfection through this computational approach.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>\n                      Following in vitro infections of pharyngeal epithelial cell lines with either IAV or\n                      <jats:italic>S. pyogenes<\/jats:italic>\n                      serotypes M1 or M49, transcriptomic changes in host cells were analyzed by RNA-seq, obtaining patterns of differentially expressed genes for each infection. These genes were then queried against the LINCS L1000 small molecule database to find compounds capable of reversing infection-induced molecular phenotypes. In this manner, we identified through computational analyses the antitumoral and antibacterial compound mitoxantrone as well as three kinase inhibitors: AT7519 and flavopiridol, which act against cyclin-dependent kinases, and BI2536, an inhibitor of the Polo-like kinase 1 (PLK1), as the main candidates to treat these coinfections.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>\n                      Using computational drug repurposing we identified four compounds that have the potential to act as suitable drugs in IAV-\n                      <jats:italic>S. pyogenes<\/jats:italic>\n                      coinfections. BI2536 and flavopiridol have been previously confirmed as active against IAV infections in vitro, while mitoxantrone is effective against\n                      <jats:italic>S. pneumoniae<\/jats:italic>\n                      . These results validate our approach, which offers a cost-effective alternative to large-scale drug screenings to find suitable candidate compounds.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1186\/s12866-026-05063-y","type":"journal-article","created":{"date-parts":[[2026,4,23]],"date-time":"2026-04-23T08:45:10Z","timestamp":1776933910000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Computational identification of novel therapeutic candidates for Streptococcus pyogenes and influenza A coinfections through transcriptomic-based drug repositioning"],"prefix":"10.1186","volume":"26","author":[{"given":"Kevin","family":"Strey","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Salem","family":"Sueto","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Georg","family":"Fuellen","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bernd","family":"Kreikemeyer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nadja","family":"Patenge","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Israel","family":"Barrantes","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2026,4,23]]},"reference":[{"issue":"6","key":"5063_CR1","doi-asserted-by":"publisher","first-page":"440","DOI":"10.1016\/j.chom.2010.05.009","volume":"7","author":"JK Taubenberger","year":"2010","unstructured":"Taubenberger JK, Kash JC. 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