title: Soluble coxsackievirus B3 3C protease inhibitor prevents cardiomyopathy in an experimental chronic myocarditis murine model.
abstract: BACKGROUND
  Coxsackievirus B3 (CVB3) is a common cause of myocarditis and dilated cardiomyopathy. CVB3 3C protease (3CP) cleaves the viral polyprotein during replication. We tested whether a water soluble 3CP inhibitor (3CPI) had antiviral effects in a chronic myocarditis model.
  
  
  METHODS
  Chronic myocarditis was established using DBA/2 strain mice. Starting on post-infection (p.i) day 3, CVB3-infected mice (n=41) were treated with 3CPI by daily intraperitoneal (i.p.) injection at a concentration of 50 μM (1.7 mg/kg/day) per day for 3 consecutive days. Additional mice (n=49) were injected with PBS as a control.
  
  
  RESULTS
  The 5-week survival rate was significantly higher with 3CPI treatment (82.3% versus 47.9%; P<0.05). Organ virus titers at day 3 and 7 and myocardial damage were significantly lower in 3CPI-treated mice. Echocardiography at day 31 indicated strong protection of heart function by 3CPI (FS, 51.2±1.5 versus 26.1±1.5%; P<0.001). Hemodynamic measurements indicated that 3CPI treatment markedly reduced CVB3-induced LV dysfunction on day 31 (dP/dTmax, 5302±352 versus 4103±408 mmHg/s, P<0.05; dP/dTmin, -3798±212 versus -2814±206 mmHg/s, P<0.01).
  
  
  CONCLUSIONS
  Water soluble 3CPI was delivered through i.p. injection after CVB3 infection. This agent preserved heart function and decreased organ viral titers and myocardial damage. Soluble 3CPI may be beneficial in the treatment of cardiomyopathy associated with enterovirus infection.
authors.affiliation: Department of Biomedical Science, Jungwon University, Goesan-gun, South Korea.
authors.forename: Byung-Kwan
authors.initials: BK
authors.lastname: Lim
authors.affiliation: Cardiac and Vascular Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Soo-Hyeon
authors.initials: SH
authors.lastname: Yun
authors.affiliation: Cardiac and Vascular Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: Eun-Seon
authors.initials: ES
authors.lastname: Ju
authors.affiliation: Department of Life Science, Gwangju Institute of Science and Technology, Gwangju, South Korea.
authors.forename: Bo-Kyoung
authors.initials: BK
authors.lastname: Kim
authors.affiliation: Cardiac and Vascular Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea.
authors.forename: You-Jung
authors.initials: YJ
authors.lastname: Lee
authors.affiliation: Center for Molecular & Cellular Imaging, Samsung Biomedical Research Institute, Seoul, South Korea.
authors.forename: Dong-Kyeom
authors.initials: DK
authors.lastname: Yoo
authors.affiliation: Department of Life Science, Gwangju Institute of Science and Technology, Gwangju, South Korea.
authors.forename: Young-Chul
authors.initials: YC
authors.lastname: Kim
authors.affiliation: Cardiac and Vascular Center, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, South Korea. Electronic address: esjeon1107@gmail.com.
authors.forename: Eun-Seok
authors.initials: ES
authors.lastname: Jeon
mesh_terms: D000086042:3C Viral Proteases; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage*; D009202:Cardiomyopathies / Q000517:prevention & control*; D003384:Coxsackievirus Infections / Q000517:prevention & control*; D003546:Cysteine Endopeptidases; D004195:Disease Models, Animal; D029822:Enterovirus B, Human / Q000187:drug effects / Q000201:enzymology*; D006321:Heart / Q000821:virology; D006334:Heart Function Tests; D008297:Male; D008811:Mice, Inbred DBA; D011480:Protease Inhibitors / Q000008:administration & dosage*; D016019:Survival Analysis; D016896:Treatment Outcome; D019562:Viral Load; D014764:Viral Proteins / Q000037:antagonists & inhibitors*
chemical_list: D000998:Antiviral Agents; D011480:Protease Inhibitors; D014764:Viral Proteins; D003546:Cysteine Endopeptidases; D000086042:3C Viral Proteases
keywords: Antiviral agent; Chronic; Coxsackievirus; Inhibitors; Myocarditis