ABSTRACT
Dengue virus type 2 (DENV-2) is an arthropod-borne deadly RNA human pathogen transmitted through the mosquito Aedes. The DENV-2 roots viral infection by facilitating entry with its envelope glycoprotein to the receptor protein Dendritic-cell-specific ICAM3-grabbing non-integrin (DC-SIGN) through membrane fusion. Here, an organizational path is reported for inhibiting the transition due to fusion activation and by blocking the residues of the DC-SIGN-E-Glyco protein complex through citrus limonoids with its antiviral effect. Based on lower binding affinity obtained with E-glycoprotein, and based on ADMET and drug-likeness study, limonin was selected as having effective interaction with DC-SIGN-E-glycoprotein complex in comparison to other citrus limonoids. The FTIR spectra performed with the limonin-E-glycoprotein sample provide evidence of hydrogen bond formation that indicates the formation of a strong limonin-E-glycoprotein conjugate. Further, the strong physical interaction between DC-SIGN and small limonin molecules in comparison to that of E-glyco with DC-SIGN assures the development of immunity against DENV-2. Supplementary Information: The online version contains supplementary material available at 10.1007/s40203-024-00207-2.