Hung P.-Y.Ho B.-C.Lee S.-Y.SUI-YUAN CHANGCHUAN-LIANG KAOSHOEI-SHENG LEELee C.-N.2020-06-182020-06-1820151932-6203https://scholars.lib.ntu.edu.tw/handle/123456789/503504Herpes simplex virus (HSV), a common latent virus in humans, causes certain severe diseases. Extensive use of acyclovir (ACV) results in the development of drug-resistant HSV strains, hence, there is an urgent need to develop new drugs to treat HSV infection. Houttuynia cordata (H. cordata), a natural herbal medicine, has been reported to exhibit anti- HSV effects which is partly NF-κB-dependent. However, the molecular mechanisms by which H. cordata inhibits HSV infection are not elucidated thoroughly. Here, we report that H. cordata water extracts (HCWEs) inhibit the infection of HSV-1, HSV-2, and acyclovirresistant HSV-1 mainly via blocking viral binding and penetration in the beginning of infection. HCWEs also suppress HSV replication. Furthermore, HCWEs attenuate the first-wave of NF-κB activation, which is essential for viral gene expressions. Further analysis of six compounds in HCWEs revealed that quercetin and isoquercitrin inhibit NF-κB activation and additionally, quercetin also has an inhibitory effect on viral entry. These results indicate that HCWEs can inhibit HSV infection through multiple mechanisms and could be a potential lead for development of new drugs for treating HSV. ? 2015 Hung et al.[SDGs]SDG3aciclovir; chlorogenic acid; glycoprotein D; Houttuynia cordata extract; Houttuynia cordata water extract; hyperin; immunoglobulin enhancer binding protein; isoquercitrin; quercetin; quercitrin; rutoside; unclassified drug; aciclovir; antivirus agent; glycoprotein D, Human herpesvirus 1; immunoglobulin enhancer binding protein; plant extract; virus envelope protein; water; animal cell; antiviral activity; antiviral resistance; Article; controlled study; drug mechanism; gene expression; herpes simplex; Herpes simplex virus 1; Herpes simplex virus 2; Houttuynia cordata; human; human cell; IE gene; molecular mechanics; nonhuman; transcription initiation; virus attachment; virus entry; virus gene; virus particle; virus replication; animal; cell line; chemistry; drug effects; gene expression regulation; genetics; heat; Houttuynia; isolation and purification; metabolism; physiology; virion; Houttuynia cordata; Human herpesvirus 1; Human herpesvirus 2; Simplexvirus; Acyclovir; Animals; Antiviral Agents; Cell Line; Drug Resistance, Viral; Gene Expression Regulation, Viral; Herpesvirus 1, Human; Herpesvirus 2, Human; Hot Temperature; Houttuynia; Humans; NF-kappa B; Plant Extracts; Viral Envelope Proteins; Virion; Virus Internalization; Virus Replication; Waterjournal article10.1371/journal.pone.0115475256432422-s2.0-84922309687