A computational approach on the interactions between sponge-derived bioactive compounds and the GTP-pocket in the methyltransferase domain of the NS5 protein from dengue virus serotype 3

• Main Authors: Pascua, Beatrice Paula G., Casiguran, Samantha Louise
• Format: text
• Language: English
• Published: Animo Repository 2023
• Subjects: Dengue viruses; Methyltransferases; Bioactive compounds; Molecular dynamics; Biochemistry; Chemistry
• Online Access: https://animorepository.dlsu.edu.ph/etdb_chem/43; https://animorepository.dlsu.edu.ph/context/etdb_chem/article/1046/viewcontent/2024_Pascua_Casiguran_A_Computational_Approach_on_the_Interactions_between_Sponge_deriv.pdf
• Institution: De La Salle University

Dengue, a mosquito-borne disease predominantly transmitted by Aedes mosquitoes, has emerged as a significant public health concern, affecting nearly half of the global population. Unfortunately, there is still no specific treatment and prevention for dengue. In line with that, bioactive compounds from marine organisms showed great potential for developing medicinal drugs as these inherit diverse biological activities. The study investigated the inhibiting potential of bioactive compounds derived from marine sponges against the methyltransferase domain in non-structural 5 (NS5) protein through in silico assays. A library composed of 50 ligands was docked to the GTP pocket which revealed that the top ten ligands had a binding free energy (BFE) ranging from -7.42 to -8.75 kcal/mol. Through pharmacophore scoring, these ligands were found to exhibit non-covalent interactions with reported conserved residues of the GTP pocket. The druglikeness of these ten ligands were assessed through ADMET profiling. The top three ligands, aragusterol B, stelletin A, and alisiaquinone C, were used and complexed with the NS5 protein for validation of these models through molecular dynamics (MD) simulations. MD simulations revealed that these models are stable and compact based on the analyses of RMSD and radius of gyration. Furthermore, high binding affinity between each ligand and the receptor was confirmed through the calculation of BFE using MMPBSA method. The energetic components of intermolecular interactions and the governing residues were also determined. Overall, the study proposes the potential of these sponge-derived compounds as drug candidates against dengue.