title: Cordycepin is a novel chemical suppressor of Epstein-Barr virus replication.
abstract: Cordyceps species are known to produce numerous active components and are used for diverse medicinal purposes because of their varied physiological activities, including their ability to protect the liver from damage as well as their anticancer, antidepressant, anti-inflammatory, hypoglycemic, antimicrobial effects. Cordycepin, an adenosine derivative, differs from adenosine in that its ribose lacks an oxygen atom at the 3' position. Several research groups have reported that cordycepin has antiviral activity against several viruses including influenza virus, plant viruses, human immunodeficiency virus(HIV), murine leukemia virus, and Epstein-Barr virus (EBV). In this study, we identify the epigenetic mechanisms by which cordycepin exerts its anti-gammaherpesvirus effects. We show that cordycepin possesses antitumor and antiviral activity against gastric carcinoma and EBV, respectively. A comparison of the CD50 values of cordycepin and its analogs showed that the lack of a 2'-hydroxyl group in cordycepin was critical for its relatively potent cytotoxicity. Cordycepin treatment decreased the rate of early apoptosis in SNU719 cells by up to 64%, but increased late apoptosis/necrosis by up to 31%. Interestingly, cordycepin increased BCL7A methylation in SNU719 cells by up to 58% and decreased demethylation by up to 37%. Consistent with these changes in methylation, cordycepin treatment significantly downregulated most EBV genes tested. Under the same conditions, cordycepin significantly decreased the frequency of Q and F promoter usage, and H3K4me3 histone enrichment was significantly reduced at several important EBV genomic loci. Extracellular and intracellular EBV genome copy numbers were reduced by up to 55% and 30%, respectively, in response to 125 μM cordycepin treatment. Finally, cordycepin significantly suppressed the transfer of EBV from LCL-EBV-GFP to AGS cells, indicating that EBV infection of gastric epithelial cells was inhibited. These results suggest that cordycepin has antiviral and antitumor activities against gammaherpesviruses and host cells latently infected with virus.
authors.affiliation: College of Pharmacy and Institute of microorganisms, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Eunhyun
authors.initials: E
authors.lastname: Ryu
authors.affiliation: College of Pharmacy and Institute of microorganisms, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Myoungki
authors.initials: M
authors.lastname: Son
authors.affiliation: College of Pharmacy and Institute of microorganisms, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Minjung
authors.initials: M
authors.lastname: Lee
authors.affiliation: Mushroom Research Division, National Institute of Horticultural and Herbal Science, Rural Development Administration, Eumseong, Republic of Korea.
authors.forename: Kanghyo
authors.initials: K
authors.lastname: Lee
authors.affiliation: Department of Genetic Engineering, Sungkyunkwan University, Suwon, Republic of Korea.
authors.forename: Jae Youl
authors.initials: JY
authors.lastname: Cho
authors.affiliation: Targeted Medicine Research Center, Korea Research Institute of Bioscience and Biotechnology, Cheongwon, Chungbuk, Republic of Korea.
authors.forename: Sungchan
authors.initials: S
authors.lastname: Cho
authors.affiliation: Research Institute of Immunobiology, Department of Biomedical Sciences, College of Medicine, The Catholic University of Korea, Seoul, Republic of Korea.
authors.forename: Suk Kyeong
authors.initials: SK
authors.lastname: Lee
authors.affiliation: College of Pharmacy and Institute of microorganisms, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: You Mie
authors.initials: YM
authors.lastname: Lee
authors.affiliation: College of Pharmacy, Duksung Women's University, Seoul, Republic of Korea.
authors.forename: Hyosun
authors.initials: H
authors.lastname: Cho
authors.affiliation: Institute for Bio-Medical Convergence, International St. Mary's Hospital, College of Medicine, Catholic Kwangdong University, Incheon, Republic of Korea.
authors.forename: Gi-Ho
authors.initials: GH
authors.lastname: Sung
authors.affiliation: College of Pharmacy and Institute of microorganisms, Kyungpook National University, Daegu, Republic of Korea.
authors.forename: Hyojeung
authors.initials: H
authors.lastname: Kang
keywords: Cordycepin; Epstein–Barr virus; antiviral agent; gastric carcinoma