The increasing threats of viral diseases have gained worldwide attention in recent years. Quite a few infectious diseases are still lack of effective prevention or treatment. The pace of developing antiviral agents could be expedited by the availability of quick and efficient drug screening platforms. In this study, quantum dot (QD) was employed to form complexes with virus and used as fluorescent imaging probes for exploring potential antiviral therapeutics. Inorganic CdSe/ZnS QDs synthesized in organic phase were encapsulated by amphiphilic alginate to attain biocompatible water-soluble QDs via phase transfer. Electrostatic repulsion force generated from both negatively-charged dengue virus (or enterovirus) and QDs were neutralized by various concentration of cationic polybrene, forming colloidal complexes of QD-virus. Results showed that susceptible cells infected with QD-tagged viruses exhibited bright fluorescence intracellularly. To demonstrate the potency of QD-tagged viruses for screening antiviral agents, susceptible cells were incubated for one hour with allophycocyanin and then infected with QD-tagged viruses. Based on the developed cell-based imaging assay, allophycocyanin with concentration of 2 mg/mL led to extremely weak intracellular fluorescence post-infection. That is, the efficacy of anti-viral activity of allophycocyanin was clearly illustrated by the inorganic-organic hybrid platform constructed in current study.