Structural elucidation and in-silico evaluation of 1,2,4-triazole derivative as potent Omicron variant of SARS-CoV-2 spike protein inhibitor with pharmacokinetics ADMET and drug-likeness predictions

Abstract

One of the most significant issues in contemporary medicine and pharmacy is the search for powerful bioactive, efficient, low-toxic anti-COVID agents. In this contrast, present work involves the synthesis of triazole derivative 6-(4-Flurophenyl)-3-(pyridine-4yl)-7H-(1,2,4)triazolo(3,4-b) (1,3,4)thiadiazine (FPTT) and its characterizations using various spectroscopic techniques (LCMS, NMR, UV-vis, FTIR). The vibrational wavenumbers were evaluated and found to be in good agreement with theoretical values. The crystal structure is determined using single crystal X-ray diffraction study and the structure is reinforced by several intra-, intermolecular and π···π interactions. These interactions result in the formation of R12(7), R33(17), S(5) and S(6) synthons which significantly contribute towards the stability of the crystal structure. Further, these interactions are validated through Hirshfeld surface and 2D fingerprint plot analysis. The C-H···N and H···H contacts are the major contributors and are in consistency with the topology and natural bond orbital results. The optimized geometrical parameters through density functional theory (DFT) are in good agreement with the experimental data. Further, various electronic properties of the compound were evaluated using the optimized structure. The molecular electrostatic potential map (MEP) and Fukui function analysis revealed the most active sites. Analysis of non-covalent interactions based on a gradient of reduced density revealed the presence of van der Waals interactions. Intrigued, by the presence of large amounts of non-covalent interactions the pharmacokinetic profiles of the compound were evaluated through ADMET provides an insight into potential inhibitors and novel drug candidates. Further in-silico studies such as molecular docking was carried out against the Omicron variant of SARS-CoV-2 spike protein with an intention to assist towards the production of improved vaccines and therapeutics.