Objective: The coxsackie and adenovirus receptor (CAR) and the decay-accelerating factor (DAF) are receptors for coxsackievirus and adenovirus, which is known as the major cause of human viral acute myocarditis and hemorrhagic conjunctivitis. Recently, it has been reported that the treatment with DAF-Fc or CAR-Fc, which are dimeric configuration by fusion of the complement-binding domain of human IgG1, could attenuate the CVB3-induced myocarditis and virus replication. We investigated the potentials as a therapeutic use of soluble virus receptors fusion proteins. In this study, We designed and generated a novel virus receptor trap (hCAR-hDAF:Fc) and a truncated virus receptor trap (hCAR_V-hDAF234:Fc) consisting of essential parts of both CVB3 receptors and the Fc portion of human IgG1, and evaluated its antiviral effects in experimental conjunctivitis. Methods and Results: Two different ���virus receptor trap���, hCAR_V-hDAF234:Fc and hCAR-hDAF:Fc, were generated using eukaryotic plasmid vector pCK. The secreted proteins of two traps in the supernatants of transfected 293T cells were quantitated by human IgG ELISA. hCAR_V-hDAF234:Fc and hCAR-hDAF:Fc in the supernatant of transfected cells neutralized adenovirus type 5 and CVB 3(H3) in a dose-dependent manner. Both soluble viral receptor proteins bound to the VP0 and VP1 capsid proteins of CVB3. For in vivo experiments, we compare adenovirus infectivity in primary rabbit conjunctiva cell, primary rabbit tenon cell and rabbit cornea cell line (SIRC). Infectivity of Ad 5 is very high in rabbit cornea cell line (SIRC). In rabbit cornea cell line, virus receptor traps neutralized adenovirus type 5 at dosage of 12.5 ng/mL. Conclusion: Our truncated soluble virus receptor trap, hCAR_V-hDAF234:Fc, attenuated viral infection in rabbit cornea cell line (SIRC). Furthermore, it consists exclusively of human components and we demonstrated that this soluble virus receptor trap may be used as a potential candidate for novel therapeutic agent for the treatment of acute viral hemorrhagic conjunctivitis during viremic phase.