title: ORI2 inhibits coxsackievirus replication and myocardial inflammation in experimental murine myocarditis.
abstract: We purified ORI2 [3-(3,4-dihydroxyphenyl)acrylic acid 1-(3,4-dihydroxyphenyl)-2-methoxycarbonylethyl ester] from an extract of the plant Isodon excisus. We tested the antiviral effect of ORI2 in a coxsackievirus-induced myocarditis model. Coxsackievirus B3 (CVB3) is a common cause of myocarditis and dilated cardiomyopathy. Activation of extracellular signal-regulated kinase (ERK) and Akt signaling in virus-infected cells is essential for CVB3 replication. Antiviral compounds were screened by HeLa cell survival assay. Several purified natural compounds were added to HeLa cells cultured in 96-well plates for 30 min after 1 multiplicity of infection (m.o.i) CVB3 infection. ORI2 significantly improved HeLa cell survival in a dose-dependent manner. For in vivo studies, BALB/c mice (n=20) were infected with CVB3, then 10 of the mice were treated by daily intraperitoneal injections of ORI2 (100 mM) for 3 consecutive days. ORI2 treatment significantly improved early survival in the treated mice compared to untreated mice (85% vs. 50%, respectively). Organ virus titers and myocardial damage were significantly lower in the ORI2-treated mice than in untreated mice. These results demonstrate that ORI2, delivered by intraperitoneal injection after CVB3 infection, has a significant antiviral effect by markedly inhibiting virus replication, resulting in a decrease in organ virus titer and myocardial damage. ORI2 may be developed as a potential therapeutic agent for the treatment of CVB3 infections.
authors.affiliation: Department of Biomedical Science, Jungwon University.
authors.forename: Byung-Kwan
authors.initials: BK
authors.lastname: Lim
authors.forename: Jin Hee
authors.initials: JH
authors.lastname: Kim
mesh_terms: D000818:Animals; D003384:Coxsackievirus Infections / Q000188:drug therapy* / Q000473:pathology; D004305:Dose-Response Relationship, Drug; D006367:HeLa Cells; D006801:Humans; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009205:Myocarditis / Q000188:drug therapy* / Q000473:pathology / Q000821:virology; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D014764:Viral Proteins / Q000502:physiology*; D014779:Virus Replication / Q000187:drug effects* / Q000502:physiology
chemical_list: D010936:Plant Extracts; D014764:Viral Proteins; C097017:coxsackie B3 virus protein 2B