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Iridoid glycosides are principal bioactive components from the <jats:italic>Gardenia jasminoides<\/jats:italic> J. Ellis fruit that exhibit antiviral activity against several strains of IAV. In the present study, we evaluated the protective effect of <jats:italic>Fructus Gardeniae<\/jats:italic> iridoid glycoside extracts (IGEs) against IAV by cytopathogenic effect(CPE), MTT and a plaque formation assay <jats:italic>in vitro<\/jats:italic> and examined the reduction in the pulmonary index (PI), restoration of body weight, reduction in mortality and increases in survival time <jats:italic>in vivo<\/jats:italic>. As a host factor, PACT provides protection against the pathogenic influenza A virus by interacting with IAV polymerase and activating the IFN-I response. To verify the whether IGEs suppress IAV replication in a PACT-dependent manner, IAV RNA replication, expression of PACT and the phosphorylation of eIF2\u03b1 in A549 cells were detected; the levels of IFN\u03b2, PACT and PKR in mouse lung tissues were determined; and the activity of IAV polymerase was evaluated in PACT-compromised cells. The results indicated that IGEs sufficiently alleviated cell damage and suppressed IAV replication <jats:italic>in vitro<\/jats:italic>, protecting mice from IAV-induced injury and lethal IAV infection. These anti-IAV effects might be related to disrupted interplay between IVA polymerase and PACT and\/or prevention of a PACT-dependent overactivated IFN-I antiviral response. Taken together, our findings reveal a new facet of the mechanisms by which IGEs fight the influenza A virus in a PACT-dependent manner.<\/jats:p>","DOI":"10.1038\/s41598-020-58443-3","type":"journal-article","created":{"date-parts":[[2020,2,5]],"date-time":"2020-02-05T11:03:18Z","timestamp":1580900598000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":25,"title":["Antiviral activity of iridoid glycosides extracted from Fructus Gardeniae against influenza A virus by PACT-dependent suppression of viral RNA replication"],"prefix":"10.1038","volume":"10","author":[{"given":"Shanshan","family":"Guo","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Bao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chun","family":"Li","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jing","family":"Sun","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ronghua","family":"Zhao","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaolan","family":"Cui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2020,2,5]]},"reference":[{"key":"58443_CR1","doi-asserted-by":"publisher","first-page":"75","DOI":"10.1016\/j.antiviral.2015.02.011","volume":"117","author":"AS Davis","year":"2015","unstructured":"Davis, A. 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