{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,27]],"date-time":"2026-02-27T00:10:25Z","timestamp":1772151025406,"version":"3.50.1"},"reference-count":31,"publisher":"Springer Science and Business Media LLC","issue":"1","license":[{"start":{"date-parts":[[2018,2,2]],"date-time":"2018-02-02T00:00:00Z","timestamp":1517529600000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"},{"start":{"date-parts":[[2018,2,2]],"date-time":"2018-02-02T00:00:00Z","timestamp":1517529600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Sci Rep"],"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Currently, many strains of influenza A virus have developed resistance against anti-influenza drugs, and it is essential to find new chemicals to combat this virus. The influenza polymerase with three proteins, PA, PB1 and PB2, is a crucial component of the viral ribonucleoprotein (RNP) complex. Here, we report the identification of a hit compound <jats:bold>221<\/jats:bold> by surface plasmon resonance (SPR) direct binding screening on the C-terminal of PA (PAC). Compound 221 can subdue influenza RNP activities and attenuate influenza virus replication. Its analogs were subsequently investigated and twelve of them could attenuate RNP activities. One of the analogs, compound 312, impeded influenza A virus replication in Madin-Darby canine kidney cells with IC<jats:sub>50<\/jats:sub> of 27.0\u2009\u00b1\u200916.8\u2009\u03bcM. <jats:italic>In vitro<\/jats:italic> interaction assays showed that compound 312 bound directly to PAC with Kd of about 40\u2009\u03bcM. Overall, the identification of novel PAC-targeting compounds provides new ground for drug design against influenza virus in the future.<\/jats:p>","DOI":"10.1038\/s41598-018-20772-9","type":"journal-article","created":{"date-parts":[[2018,1,29]],"date-time":"2018-01-29T14:44:23Z","timestamp":1517237063000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Identification of influenza polymerase inhibitors targeting C-terminal domain of PA through surface plasmon resonance screening"],"prefix":"10.1038","volume":"8","author":[{"given":"Chun-Yeung","family":"Lo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Olive Tin-Wai","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Wen-Ping","family":"Tang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun","family":"Hu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Guo Xin","family":"Wang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jacky Chi-Ki","family":"Ngo","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"David Chi-Cheong","family":"Wan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Leo Lit-Man","family":"Poon","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Pang-Chui","family":"Shaw","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2018,2,2]]},"reference":[{"key":"20772_CR1","unstructured":"WHO. 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