The study employs density functional theory (DFT) to examine the drug-loading efficiency of graphyne (GYN) as a vehicle for the Tioguanine (TG) drug. The researchers analyzed the interaction energy, electrical properties of pure GYN, TG molecules, and TG@GYN complex to determine their effectiveness as a carrier. Configuration a, which utilized nitrogen and sulfur atoms in interactions, was deemed the most suitable among the three considered TG sites. Gas-phase interaction between TG drug and GYN resulted in an energy of adsorption about -1.64 eV. The study utilized non-covalent interaction (NCI) analysis to assess the interaction between GYN and TG drug, indicating weak forces of interaction in the TG@GYN complex. The HOMO-LUMO and charge-decomposition analysis described the transfer of charge from TG molecules to pure GYN during formation of TG@GYN. The results suggest that GYN could function as a promising candidate for carrying and delivering TG drug, leading to further research into similar 2D nanomaterials for drug transport applications.
Dengue virus Type 2 (DENV-2) is predominant serotype causing major dengue epidemics. There are a number of studies carried out to find its effective antiviral, however to date, there is still no molecule either from peptide or small molecules released as a drug. The present study aims to identify small molecules inhibitor from National Cancer Institute database through virtual screening. One of the hits, D0713 (IC50 = 62 μM) bearing thioguanine scaffold was derivatised into 21 compounds and evaluated for DENV-2 NS2B/NS3 protease inhibitory activity. Compounds 18 and 21 demonstrated the most potent activity with IC50 of 0.38 μM and 16 μM, respectively. Molecular dynamics and MM/PBSA free energy of binding calculation were conducted to study the interaction mechanism of these compounds with the protease. The free energy of binding of 18 calculated by MM/PBSA is -16.10 kcal/mol compared to the known inhibitor, panduratin A (-11.27 kcal/mol), which corroborates well with the experimental observation. Results from molecular dynamics simulations also showed that both 18 and 21 bind in the active site and stabilised by the formation of hydrogen bonds with Asn174.