Abstract In the face of the ongoing threat of dengue fever to global public health, exploring the potential of deep‐sea natural resources could lead to significant breakthroughs in combating the dengue virus. This study focused on screening natural compounds from the sponge Rhabdastrella providentiae using molecular docking simulations via the AutoDock Vina v1.2.3 program. Remarkably, two compounds, rhabdastrellin G and rhabdastrellin I, demonstrated strong affinity for the target protein dengue virus serotype 2 RNA‐dependent RNA polymerase, with Δ G values of −9.034 and −8.133 kcal/mol, surpassing the binding affinity of the reference inhibitor (−7.51 kcal/mol). Further molecular dynamics simulations were conducted to examine the structural stability of these complexes, revealing that both rhabdastrellin G and rhabdastrellin I maintained stable binding with the dengue virus serotype 2 RNA dependent RNA polymerase protein throughout the 50 ns simulation period. Additionally, ADMET evaluations indicated that these compounds exhibit high intestinal absorption, lack hepatotoxicity, skin sensitization, and AMES toxicity, and do not inhibit hERG channels I and II. Consequently, rhabdastrellin G and rhabdastrellin I emerge as promising candidates for inhibiting dengue virus serotype 2 RNA dependent RNA polymerase and could potentially serve as effective antiviral agents against dengue fever.
Ha et al. (Wed,) studied this question.