Wang S.-Y.Tseng C.-P.Tsai K.-C.Lin C.-F.Wen C.-Y.Tsay H.-S.Sakamoto N.CHIN-HSIAO TSENGCheng J.-C.2020-06-012020-06-0120090006-291Xhttps://www.scopus.com/inward/record.uri?eid=2-s2.0-67349091694&doi=10.1016%2fj.bbrc.2009.05.043&partnerID=40&md5=e8803187fcbf5ed48767725fe5dcbd38https://scholars.lib.ntu.edu.tw/handle/123456789/496158Chronic hepatitis C virus (HCV) infection is a worldwide public issue. In this study, we performed bioactivity-guided screening of the Lonicera hypoglauca Miq. crude extracts to find for naturally chemical entities with anti-HCV activity. Pheophytin a was identified from the ethanol-soluble fraction of L. hypoglauca that elicited dose-dependent inhibition of HCV viral proteins and RNA expression in both replicon cells and cell culture infectious system. Computational modeling revealed that pheophytin a can bind to the active site of HCV-NS3, suggesting that NS3 is a potent molecular target of pheophytin a. Biochemical analysis further revealed that pheophytin a inhibited NS3 serine protease activity with IC50 = 0.89 μM. Notably, pheophytin a and IFNα-2a elicited synergistic anti-HCV activity in replicon cells with no significant cytotoxicity. This study thereby demonstrates for the first time that pheophytin a is a potent HCV-NS3 protease inhibitor and offers insight for development of novel anti-HCV regimens. ? 2009 Elsevier Inc. All rights reserved.[SDGs]SDG3alpha2a interferon; antivirus agent; nonstructural protein 3; pheophytin a; plant extract; serine proteinase; unclassified drug; virus protein; virus RNA; antiviral activity; article; cell culture; cell survival; cell viability; concentration response; controlled study; drug cytotoxicity; drug potency; drug potentiation; drug protein binding; drug screening; enzyme inhibition; gene expression; Hepatitis C virus; human; human cell; hydrogen bond; IC 50; Lonicera hypoglauca; medicinal plant; molecular model; nonhuman; plant leaf; plant stem; priority journal; protein expression; replicon; Antiviral Agents; Catalytic Domain; Cell Line; Computer Simulation; Drug Evaluation, Preclinical; Hepacivirus; Humans; Interferon Alfa-2a; Lonicera; Models, Molecular; Pheophytins; Viral Nonstructural Proteins; Viral Proteins; Virus Replication; Hepatitis C virus; Lonicerajournal article10.1016/j.bbrc.2009.05.043194505562-s2.0-67349091694