De-Novo drug design of novel 1,2,3–triazole-naphthamide as an inhibitor of SARS-Cov-2 main protease: Synthesis, bioinformatics and biophysical studies

Abstract

A novel 1,2,3-triazole-napthamide molecule (SSAM-1) is designed as per De-Novo drug design method and synthesized by using copper-catalyzed alkyne-azide cycloaddition reaction. The interaction studies of SSAM-1 with bovine serum albumin (BSA), human serum albumin (HSA) and bromelain (BMLN) are investigated by steady state fluorescence spectroscopic studies. The experimental results for these interaction studies are validated by molecular docking method. The theoretical prediction of ADMET properties of SSAM-1 are also performed using computational methods. All these studies indicate significant and spontaneous binding of SSAM-1 with serum albumins and BMLN at pH 7 under varying temperature conditions (288K, 298K, 308K). In all the three cases the interaction of the molecule with the proteins and enzymes led to quenching of the fluorescence emission (mainly via static quenching mechanism) of tryptophan (Trp) residue present in the proteins and in the enzyme. The complexation with SSAM-1 changes the microenvironment of the Trp residue(s) of BSA, HSA and BMLN. Strong binding affinity between proteins and SSAM-1 is indicated by the binding constant values, which is in 103-105 orders. Hydrophobic forces are acting as the major interacting forces for SSAM-1-HSA interaction while H-bonding and van der Waals forces are acting as the primary interacting forces for SSAM-1 interacting with BSA and BMLN. ADMET prediction reveals the drug-able nature of SSAM-1 which is justified due to its ability to bind with the serum albumins. In addition binding study of SSAM-1 with BMLN indicates its possibility of oral administration. Conducting such binding studies of the newly synthesized triazole with biomolecules, an effort is made to assess the contribution of a novel compound to the development of medicines for the drug design process at a very early stage of the research.