{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T16:17:07Z","timestamp":1790957827082,"version":"4.1.0"},"reference-count":42,"publisher":"MDPI AG","issue":"5","license":[{"start":{"date-parts":[[2019,5,22]],"date-time":"2019-05-22T00:00:00Z","timestamp":1558483200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81573471, 81603341, 81872908"],"award-info":[{"award-number":["81573471, 81603341, 81872908"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"name":"the Key Laboratory of Virology of Guangzhou","award":["201705030003"],"award-info":[{"award-number":["201705030003"]}]},{"name":"Guangzhou Major program of the Industry-University-Research collaborative innovation","award":["201704030087"],"award-info":[{"award-number":["201704030087"]}]},{"name":"Guangzhou Major program of the Industry-University-Research collaborative innovation","award":["201604020178"],"award-info":[{"award-number":["201604020178"]}]},{"name":"the Scientific Research Foundation of Shenzhen University for the Newly Introduced Teacher","award":["2018021"],"award-info":[{"award-number":["2018021"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Viruses"],"abstract":"<jats:p>Infection of Herpes simplex virus 1 (HSV-1) induces severe clinical disorders, such as herpes simplex encephalitis and keratitis. Acyclovir (ACV) is the current therapeutic drug against viral infection and ACV-resistant strains have gradually emerged, leading to the requirement for novel antiviral agents. In this study, we exhibited the antiviral activity of amentoflavone, a naturally occurring biflavonoid, toward HSV-1 and ACV-resistant strains. Amentoflavone significantly inhibited infection of HSV-1 (F strain), as well as several ACV-resistant strains including HSV-1\/106, HSV-1\/153 and HSV-1\/Blue at high concentrations. Time-of-drug-addition assay further revealed that amentoflavone mainly impaired HSV-1 early infection. More detailed study demonstrated that amentoflavone affected cofilin-mediated F-actin reorganization and reduced the intracellular transportation of HSV-1 from the cell membrane to the nucleus. In addition, amentoflavone substantially decreased transcription of viral immediate early genes. Collectively, amentoflavone showed strong antiviral activity against HSV-1 and ACV-resistant strains, and amentoflavone could be a promising therapeutic candidate for HSV-1 pathogenesis.<\/jats:p>","DOI":"10.3390\/v11050466","type":"journal-article","created":{"date-parts":[[2019,5,23]],"date-time":"2019-05-23T03:22:03Z","timestamp":1558581723000},"page":"466","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Amentoflavone Inhibits HSV-1 and ACV-Resistant Strain Infection by Suppressing Viral Early Infection"],"prefix":"10.3390","volume":"11","author":[{"given":"Feng","family":"Li","sequence":"first","affiliation":[{"name":"Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaowei","family":"Song","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Guifeng","family":"Su","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yiliang","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zhaoyang","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jiaoyan","family":"Jia","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shurong","family":"Qing","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lianzhou","family":"Huang","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuan","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9275-1239","authenticated-orcid":false,"given":"Kai","family":"Zheng","sequence":"additional","affiliation":[{"name":"School of Pharmaceutical Sciences, Health Science Center, Shenzhen University, Shenzhen 518060, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9918-2865","authenticated-orcid":false,"given":"Yifei","family":"Wang","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine, College of Life Science and Technology, Jinan University, Guangzhou 510632, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2019,5,22]]},"reference":[{"key":"ref_1","first-page":"85","article-title":"Application of real-time pcr assay for investigating the presence of herpes simplex virus type 1 DNA","volume":"62","author":"Midaksiewirska","year":"2010","journal-title":"Med. Dosw. Mikrobiol."},{"key":"ref_2","first-page":"1577","article-title":"Herpes simplex encephalitis","volume":"101","author":"Kennedy","year":"1981","journal-title":"Tidsskr. Den Nor. L\u00e6geforen. Tidsskr. Prakt. Med. Ny R\u00e6kke"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"219","DOI":"10.1016\/0889-1591(91)90018-6","article-title":"Stress-related activation of epstein-barr virus","volume":"5","author":"Glaser","year":"1991","journal-title":"Brain Behav. Immun."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"131","DOI":"10.3233\/JAD-170966","article-title":"HSV-1-specific igg subclasses distribution and serum neutralizing activity in alzheimer\u2019s disease and in mild cognitive impairment","volume":"63","author":"Agostini","year":"2018","journal-title":"J. Alzheimer\u2019s Dis."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"2735","DOI":"10.1016\/j.bmcl.2007.02.079","article-title":"Imidazo[1,2-]pyridines with potent activity against herpesviruses","volume":"17","author":"Gudmundsson","year":"2007","journal-title":"Bioorg. Med. Chem. Lett."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"868","DOI":"10.1128\/AAC.42.4.868","article-title":"Survey of resistance of herpes simplex virus to acyclovir in northwest england","volume":"42","author":"Christophers","year":"1998","journal-title":"Antimicrob. Agents Chemother."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"229","DOI":"10.2217\/fvl.12.137","article-title":"Viral interactions with microtubules: Orchestrators of host cell biology?","volume":"8","author":"Brice","year":"2013","journal-title":"Future Virol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"387","DOI":"10.1111\/j.1462-5822.2005.00679.x","article-title":"Viral interactions with the cytoskeleton: A hitchhiker\u2019s guide to the cell","volume":"8","author":"Radtke","year":"2006","journal-title":"Cell Microbiol."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"426","DOI":"10.1016\/j.tim.2007.08.003","article-title":"Actin and rho gtpases in herpesvirus biology","volume":"15","author":"Favoreel","year":"2007","journal-title":"Trends Microbiol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1083\/jcb.201103148","article-title":"Pathogens and polymers: Microbe-host interactions illuminate the cytoskeleton","volume":"195","author":"Haglund","year":"2011","journal-title":"J. Cell Boil."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"782","DOI":"10.1016\/j.cell.2008.06.036","article-title":"HIV envelope-cxcr4 signaling activates cofilin to overcome cortical actin restriction in resting cd4 t cells","volume":"134","author":"Yoder","year":"2008","journal-title":"Cell"},{"key":"ref_12","first-page":"677","article-title":"Pathogenic microbes manipulate cofilin activity to subvert actin cytoskeleton","volume":"42","author":"Zheng","year":"2016","journal-title":"Crit. Rev. Microbiol."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"e00958-13","DOI":"10.1128\/mBio.00958-13","article-title":"Epidermal growth factor receptor-pi3k signaling controls cofilin activity to facilitate herpes simplex virus 1 entry into neuronal cells","volume":"5","author":"Zheng","year":"2014","journal-title":"mBio"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1002\/rmv.1796","article-title":"Viruses exploit the function of epidermal growth factor receptor","volume":"24","author":"Zheng","year":"2014","journal-title":"Rev. Med. Virol."},{"key":"ref_15","doi-asserted-by":"crossref","unstructured":"Jin, F., Ma, K., Chen, M., Zou, M., Wu, Y., Li, F., and Wang, Y. (2015). Pentagalloylglucose blocks the nuclear transport and nucleocapsid egress process to inhibit hsv-1 infection. Jpn. J. Infect. Dis., 69.","DOI":"10.7883\/yoken.JJID.2015.137"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1007\/BF02974043","article-title":"Anti-herpetic activity of various medicinal plant extracts","volume":"20","author":"Woo","year":"1997","journal-title":"Arch. Pharmacal. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"8348","DOI":"10.1021\/acs.jafc.7b02867","article-title":"Using ultra-performance liquid chromatography quadrupole time of flight mass spectrometry-based chemometrics for the identification of anti-angiogenic biflavonoids from edible garcinia species","volume":"65","author":"Li","year":"2017","journal-title":"J. Agric. Food Chem."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"6596","DOI":"10.1021\/jf070257h","article-title":"Flavonoids and biflavonoids in tuscan berries of juniperus communis l.: Detection and quantitation by hplc\/dad\/esi\/ms","volume":"55","author":"Marzia","year":"2007","journal-title":"J. Agric. Food Chem."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"1957","DOI":"10.1021\/jf5019615","article-title":"Liquid chromatography-tandem mass spectrometry determination and pharmacokinetic analysis of amentoflavone and its conjugated metabolites in rats","volume":"63","author":"Sha","year":"2015","journal-title":"J. Agric. Food Chem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"1125","DOI":"10.4103\/1673-5374.160109","article-title":"Amentoflavone protects hippocampal neurons: Anti-inflammatory, antioxidative, and antiapoptotic effects","volume":"10","author":"Zhang","year":"2015","journal-title":"Neural Regen. Res."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"87","DOI":"10.1007\/s11010-015-2641-6","article-title":"Amentoflavone protects against psoriasis-like skin lesion through suppression of nf-\u03bab-mediated inflammation and keratinocyte proliferation","volume":"413","author":"An","year":"2016","journal-title":"Mol. Cell. Biochem."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"96","DOI":"10.1016\/j.lfs.2017.09.026","article-title":"Amentoflavone suppresses tumor growth in ovarian cancer by modulating skp2","volume":"189","author":"Liu","year":"2017","journal-title":"Life Sci."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1248\/bpb.24.311","article-title":"Antiviral amentoflavone from selaginella sinensis","volume":"24","author":"Ma","year":"2001","journal-title":"Boil. Pharm. Bull."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"120","DOI":"10.1055\/s-1999-13971","article-title":"Antiviral activities of biflavonoids","volume":"65","author":"Lin","year":"1999","journal-title":"Planta Med."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1007\/s00705-011-1164-z","article-title":"Inhibition of fatty acid synthase by amentoflavone reduces coxsackievirus b3 replication","volume":"157","author":"Wilsky","year":"2012","journal-title":"Arch Virol."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"8440","DOI":"10.1128\/JVI.00609-12","article-title":"Cofilin 1-mediated biphasic f-actin dynamics of neuronal cells affect herpes simplex virus 1 infection and replication","volume":"86","author":"Xiang","year":"2012","journal-title":"J. Virol."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"65","DOI":"10.1186\/s10020-018-0066-x","article-title":"Heat-shock protein 90alpha is involved in maintaining the stability of vp16 and vp16-mediated transactivation of alpha genes from herpes simplex virus-1","volume":"24","author":"Wang","year":"2018","journal-title":"Mol. Med."},{"key":"ref_28","doi-asserted-by":"crossref","unstructured":"Liu, X., Main, D., Ma, Y., and He, B. (2018). Herpes simplex virus 1 inhibits tank-binding kinase 1 through formation of the us11-hsp90 complex. J. Virol.","DOI":"10.1128\/JVI.00402-18"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"447","DOI":"10.1016\/S0166-3542(02)00077-3","article-title":"Antiherpes simplex virus type 2 activity of casuarinin from the bark of terminalia arjuna linn","volume":"55","author":"Cheng","year":"2002","journal-title":"Antivir. Res."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1093\/oxfordjournals.aje.a118408","article-title":"A simple method of estimating fifty per cent endpoints","volume":"27","author":"Reed","year":"1938","journal-title":"Am J Epidemiol."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"260","DOI":"10.2144\/03342bm05","article-title":"Titration of non-occluded baculovirus using a cell viability assay","volume":"34","author":"Mena","year":"2003","journal-title":"Biotechniques"},{"key":"ref_32","first-page":"397","article-title":"Hsp90 inhibitor at-533 blocks hsv-1 nuclear egress and assembly","volume":"164","author":"Li","year":"2018","journal-title":"J. Biochem."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"186","DOI":"10.1016\/j.bbrc.2011.01.006","article-title":"Autophagy is involved in anti-viral activity of pentagalloylglucose (pgg) against herpes simplex virus type 1 infection in vitro","volume":"405","author":"Pei","year":"2011","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"421","DOI":"10.1016\/S0140-6736(82)91620-8","article-title":"Isolation and characterisation of resistant herpes simplex virus after acyclovir therapy","volume":"319","author":"Burns","year":"1982","journal-title":"Lancet"},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Jin, F., Li, S., Zheng, K., Zhuo, C., Ma, K., Chen, M., Wang, Q., Zhang, P., Fan, J., and Ren, Z. (2014). Silencing herpes simplex virus type 1 capsid protein encoding genes by sirna: A promising antiviral therapeutic approach. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0096623"},{"key":"ref_36","doi-asserted-by":"crossref","unstructured":"Zhong, M., Zheng, K., Chen, M., Xiang, Y., Jin, F., Ma, K., Qiu, X., Wang, Q., Peng, T., and Kitazato, K. (2014). Heat-shock protein 90 promotes nuclear transport of herpes simplex virus 1 capsid protein by interacting with acetylated tubulin. PLoS ONE, 9.","DOI":"10.1371\/journal.pone.0099425"},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"294","DOI":"10.1016\/S0968-0004(03)00088-4","article-title":"The herpes simplex virus vp16-induced complex: The makings of a regulatory switch","volume":"28","author":"Wysocka","year":"2003","journal-title":"Trends Biochem. Sci."},{"key":"ref_38","first-page":"349","article-title":"Study on the inhibitory action on cvb3 replication in vitro by the extracts from selaginella moelledorfii hieron","volume":"29","author":"Yin","year":"2009","journal-title":"Chin. J. Hosp. Pharm."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"1007","DOI":"10.1083\/jcb.136.5.1007","article-title":"Microtubule-mediated transport of incoming herpes simplex virus 1 capsids to the nucleus","volume":"136","author":"Sodeik","year":"1997","journal-title":"J. Cell Boil."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Youn, K.J., Angelo, M., Chao, M.V., Ian, M., and Wilson, A.C. (2012). Transient reversal of episome silencing precedes vp16-dependent transcription during reactivation of latent hsv-1 in neurons. PLoS Pathog., 8.","DOI":"10.1371\/journal.ppat.1002540"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1016\/j.chom.2006.12.001","article-title":"Hsv-1 icp34.5 confers neurovirulence by targeting the beclin 1 autophagy protein","volume":"1","author":"Orvedahl","year":"2007","journal-title":"Cell Host Microbe"},{"key":"ref_42","first-page":"27","article-title":"Amentoflavone induces autophagy and modulates p53","volume":"21","author":"Park","year":"2019","journal-title":"Cell J."}],"container-title":["Viruses"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1999-4915\/11\/5\/466\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T12:54:18Z","timestamp":1760187258000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1999-4915\/11\/5\/466"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,5,22]]},"references-count":42,"journal-issue":{"issue":"5","published-online":{"date-parts":[[2019,5]]}},"alternative-id":["v11050466"],"URL":"https:\/\/doi.org\/10.3390\/v11050466","relation":{},"ISSN":["1999-4915"],"issn-type":[{"value":"1999-4915","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,5,22]]}}}