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Hybrid natural products produced via mixed biosynthetic pathways are unique and often surprise one with unexpected medicinal properties in addition to their fascinating structural complexity/diversity. In view of chemical structures, hybridization is a way of diversifying natural products usually through dimerization of two similar or dissimilar subcomponents through a C–C or N–C covalent linkage. Here, we report four structurally attractive diterpene–alkaloid conjugates polyalongarins A–D (<b>1</b>–<b>4</b>), clerodane-containing aporphine and proaporphine alkaloids, the first of its kind from the barks of Taiwanese <i>Polyalthia longifolia</i> (Sonn.) Thwaites var. <i>pendula</i>. In addition to conventional spectroscopic analysis, single crystal X-ray crystallography was employed to determine the chemical structures and stereo-configurations of <b>1</b>. Compounds <b>1</b>–<b>4</b> were subsequently subjected to in vitro antiviral examination against DENV2 by evaluating the expression level of the NS2B protein in DENV2-infected Huh-7 cells. These compounds display encouraging anti-DENV2 activity with superb EC₅₀ (2.8–6.4 μM) and CC₅₀ values (50.4–200 μM). The inhibitory mechanism of <b>1</b>–<b>4</b> on NS2B was further explored drawing on in-silico molecular docking analysis. Based on calculated binding affinities and predicted interactions between the functional groups of <b>1</b>–<b>4</b> and the allosteric-site residues of the DENV2 NS2B-NS3 protease, our analysis concludes that the clerodane–aporphine/proaporphine-type hybrids are novel and effective DENV NS2B-NS3 protease inhibitors.