{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T20:26:12Z","timestamp":1790108772901,"version":"4.0.1"},"reference-count":35,"publisher":"MDPI AG","issue":"23","license":[{"start":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T00:00:00Z","timestamp":1638403200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Molecules"],"abstract":"<jats:p>Drug repurposing can quickly and effectively identify novel drug repurposing opportunities. The PA endonuclease catalytic site has recently become regarded as an attractive target for the screening of anti-influenza drugs. PA N-terminal (PAN) inhibitor can inhibit the entire PA endonuclease activity. In this study, we screened the effectivity of PAN inhibitors from the FDA database through in silico methods and in vitro experiments. PAN and mutant PAN-I38T were chosen as virtual screening targets for overcoming drug resistance. Gel-based PA endonuclease analysis determined that the drug lifitegrast can effectively inhibit PAN and PAN-I38T, when the IC50 is 32.82 \u00b1 1.34 \u03bcM and 26.81 \u00b1 1.2 \u03bcM, respectively. Molecular docking calculation showed that lifitegrast interacted with the residues around PA or PA-I38 T\u2019s active site, occupying the catalytic site pocket. Both PAN\/PAN-I38T and lifitegrast can acquire good equilibrium in 100 ns molecular dynamic simulation. Because of these properties, lifitegrast, which can effectively inhibit PA endonuclease activity, was screened through in silico and in vitro research. This new research will be of significance in developing more effective and selective drugs for anti-influenza therapy.<\/jats:p>","DOI":"10.3390\/molecules26237326","type":"journal-article","created":{"date-parts":[[2021,12,2]],"date-time":"2021-12-02T21:19:08Z","timestamp":1638479948000},"page":"7326","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Drug Repurposing for Influenza Virus Polymerase Acidic (PA) Endonuclease Inhibitor"],"prefix":"10.3390","volume":"26","author":[{"given":"Xin","family":"Meng","sequence":"first","affiliation":[{"name":"School of Life Science, Jilin University, No. 2699 Qianjin Street, Changchun 130012, China"},{"name":"School of Life Science, Jilin Normal University, Siping 136000, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9201-5872","authenticated-orcid":false,"given":"Ye","family":"Wang","sequence":"additional","affiliation":[{"name":"School of Life Science, Jilin University, No. 2699 Qianjin Street, Changchun 130012, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2021,12,2]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1001\/jama.289.2.179","article-title":"Mortality associated with influenza and respiratory syncytial virus in the United States","volume":"289","author":"Thompson","year":"2003","journal-title":"JAMA"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1285","DOI":"10.1016\/S0140-6736(17)33293-2","article-title":"Estimates of global seasonal influenza-associated respiratory mortality: A modelling study","volume":"391","author":"Iuliano","year":"2018","journal-title":"Lancet"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1038\/nature06945","article-title":"The genomic and epidemiological dynamics of human influenza A virus","volume":"453","author":"Rambaut","year":"2008","journal-title":"Nature"},{"key":"ref_4","doi-asserted-by":"crossref","unstructured":"De Vlugt, C., Sikora, D., and Pelchat, M. 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