GNF-2-deg is a PROTAC degrader that targets the envelope protein of the dengue virus (DENV E protein), achieving a DC50 of 0.83 μM. It inhibits viral entry by preventing membrane fusion mediated by the E protein and demonstrates antiviral activity against DENV 2 through protein degradation, with an EC90 of 3.5 μM. Additionally, GNF-2-deg shows antiviral efficacy against ZIKV, JEV, WNV, and YFV, with EC90 values ranging from 1.96 to 7.79 μM.