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Updated: Aug 7, 2026
Use of Viral Entry Assays and Molecular Docking Analysis for the Identification of Antiviral Candidates against Coxsackievirus A16
Published on: July 15, 2019
Virus receptor trap neutralizes coxsackievirus in experimental murine viral myocarditis
Byung-Kwan Lim1, Jin-Ho Choi, Jae-Hwan Nam
1Department of Medicine, Sungkyunkwan University School of Medicine, Cardiac and Vascular Center, Samsung Medical Center, 50 Il-won Dong, Kangnam-Ku, Seoul 135-710, Korea.
Objective:
The coxsackie and adenovirus receptor (CAR) and the decay-accelerating factor (DAF) are receptors for coxsackievirus B3 (CVB3), which is known as the major cause of human viral myocarditis. We investigated the potential for therapeutic use of soluble virus receptor fusion proteins.
Methods:
We designed and generated a novel virus receptor trap (hCAR-hDAF:Fc) consisting of both CVB3 receptors and the Fc portion of human IgG1 and evaluated its antiviral effects in experimental CVB3 myocarditis.
Results:
Among four soluble virus receptor fusion proteins (hCAR:Fc, hDAF:Fc, hCAR-hDAF:Fc and hDAF-hCAR:Fc), hCAR:Fc and hCAR-hDAF:Fc in the supernatant of transfected cells neutralized echovirus, adenovirus, and various serotypes of CVB in a dose-dependent manner. Both soluble viral receptor proteins bound to the VP0 and VP1 capsid proteins of CVB3. The in vivo efficacy of viral receptor proteins was evaluated by intramuscular injection of plasmid (hCAR:Fc or hCAR-hDAF:Fc) followed by electroporation in a murine model of CVB3 myocarditis. Serum levels of the virus receptor proteins increased relative to baseline values from day 3 and peaked on day 14 at 12.9-fold for hCAR:Fc and 7.1-fold for hCAR-hDAF:Fc. The 3-week survival rate was significantly higher in hCAR-hDAF:Fc-treated mice (61%) than in hCAR:Fc-treated mice (29%) and in controls (15%; p<0.05). Myocardial inflammation, fibrosis, and myocardial virus titers were all significantly reduced in the hCAR:Fc and hCAR-hDAF:Fc groups compared to the controls.
Conclusion:
Our soluble virus receptor trap, hCAR-hDAF:Fc, attenuated viral infection, myocardial inflammation, and fibrosis, resulting in higher survival rates in mice with coxsackieviral myocarditis. Furthermore, it consists exclusively of human components, and we demonstrated that this soluble virus receptor trap may be used as a potential candidate for a novel therapeutic agent for the treatment of acute viral myocarditis during the viremic phase.
Insights
A novel soluble virus receptor trap, hCAR-hDAF:Fc, effectively neutralized coxsackievirus B3 (CVB3) and reduced inflammation in mice. This therapeutic agent shows promise for treating viral myocarditis.
Area of Science:
- Virology
- Immunology
- Cardiovascular Research
Background:
- Coxsackievirus B3 (CVB3) is a primary cause of viral myocarditis.
- The coxsackie and adenovirus receptor (CAR) and decay-accelerating factor (DAF) are key receptors for CVB3 entry.
Purpose of the Study:
- To investigate the therapeutic potential of soluble virus receptor fusion proteins.
- To evaluate a novel virus receptor trap, hCAR-hDAF:Fc, for treating CVB3-induced myocarditis.
Main Methods:
- Designed and generated a soluble virus receptor trap (hCAR-hDAF:Fc) comprising human CAR, DAF, and IgG1 Fc portion.
- Assessed antiviral neutralization of echovirus, adenovirus, and CVB serotypes in vitro.
- Evaluated in vivo efficacy in a murine model of CVB3 myocarditis via plasmid injection and electroporation.
Main Results:
- hCAR-hDAF:Fc and hCAR:Fc neutralized various viruses in a dose-dependent manner.
- In vivo, hCAR-hDAF:Fc treatment significantly increased survival rates (61%) compared to controls (15%) in a murine myocarditis model.
- Myocardial inflammation, fibrosis, and viral titers were significantly reduced in treated groups.
Conclusions:
- The soluble virus receptor trap hCAR-hDAF:Fc attenuated viral infection, inflammation, and fibrosis in coxsackieviral myocarditis.
- This human-component-only therapeutic agent represents a potential candidate for acute viral myocarditis treatment during the viremic phase.
