{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,6,3]],"date-time":"2026-06-03T19:12:19Z","timestamp":1780513939068,"version":"3.54.1"},"reference-count":30,"publisher":"MDPI AG","issue":"6","license":[{"start":{"date-parts":[[2022,6,5]],"date-time":"2022-06-05T00:00:00Z","timestamp":1654387200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"National Natural Science Foundation of China","award":["81773631"],"award-info":[{"award-number":["81773631"]}]},{"name":"National Natural Science Foundation of China","award":["81900402"],"award-info":[{"award-number":["81900402"]}]},{"name":"National Natural Science Foundation of China","award":["2018 ZX09711003"],"award-info":[{"award-number":["2018 ZX09711003"]}]},{"name":"National Science and Technology Major Projects for \u201cMajor New Drugs Innovation and Development","award":["81773631"],"award-info":[{"award-number":["81773631"]}]},{"name":"National Science and Technology Major Projects for \u201cMajor New Drugs Innovation and Development","award":["81900402"],"award-info":[{"award-number":["81900402"]}]},{"name":"National Science and Technology Major Projects for \u201cMajor New Drugs Innovation and Development","award":["2018 ZX09711003"],"award-info":[{"award-number":["2018 ZX09711003"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Flaviviruses, represented by Zika and dengue virus (ZIKV and DENV), are widely present around the world and cause various diseases with serious consequences. However, no antiviral drugs have been clinically approved for use against them. Azelnidipine (ALP) is a dihydropyridine calcium channel blocker and has been approved for use as an antihypertensive drug. In the present study, ALP was found to show potent anti-flavivirus activities in vitro and in vivo. ALP effectively prevented the cytopathic effect induced by ZIKV and DENV and inhibited the production of viral RNA and viral protein in a dose-dependent manner. Moreover, treatment with 0.3 mg\/kg of ALP protected 88.89% of mice from lethal challenge. Furthermore, using the time-of-drug-addition assay, the enzymatic inhibition assay, the molecular docking, and the surface plasmon resonance assay, we revealed that ALP acted at the replication stage of the viral infection cycle by targeting the viral RNA-dependent RNA polymerase. These findings highlight the potential for the use of ALP as an antiviral agent to combat flavivirus infections.<\/jats:p>","DOI":"10.3390\/v14061228","type":"journal-article","created":{"date-parts":[[2022,6,5]],"date-time":"2022-06-05T10:47:11Z","timestamp":1654426031000},"page":"1228","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":9,"title":["Azelnidipine Exhibits In Vitro and In Vivo Antiviral Effects against Flavivirus Infections by Targeting the Viral RdRp"],"prefix":"10.3390","volume":"14","author":[{"given":"Zhuang","family":"Wang","sequence":"first","affiliation":[{"name":"Institute of Medical Research, Northwestern Polytechnical University, Xi\u2019an 710072, China"},{"name":"National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunzheng","family":"Yan","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Qingsong","family":"Dai","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yijie","family":"Xu","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiye","family":"Yin","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wei","family":"Li","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuexiang","family":"Li","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaotong","family":"Yang","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojia","family":"Guo","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Miaomiao","family":"Liu","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xingjuan","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Medical Research, Northwestern Polytechnical University, Xi\u2019an 710072, China"},{"name":"National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ruiyuan","family":"Cao","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0536-620X","authenticated-orcid":false,"given":"Wu","family":"Zhong","sequence":"additional","affiliation":[{"name":"National Engineering Research Center for the Emergency Drug, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2022,6,5]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"796","DOI":"10.1038\/s41564-020-0714-0","article-title":"The continued threat of emerging flaviviruses","volume":"5","author":"Pierson","year":"2020","journal-title":"Nat. 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