Tenofovir antiviral drug solubility enhancement with B-cyclodextrin inclusion complex and in silico study of potential inhibitor against SARS-CoV-2 main protease (Mpro)

Tenofovir (TFR) is an antiviral drug commonly used to fight against viral diseases infection due to its good potency and high genetic barrier to drug resistance. In physiological conditions, TFR is less water soluble, more unstable, and less permeable, limiting its effective therapeutic applications. In addition to their use in treating the Coronavirus disease 2019 (COVID-19), cyclodextrins (CDs) are also being used as a mole-cule to develop therapies for other diseases due to its enhance solubility and stability. This study is designed to synthesize and characterization of B-CD:TFR inclusion complex and its interaction against SARS-CoV-2 (MPro) protein (PDB ID;7cam). Several techniques were used to characterize the prepared B-CD:TFR inclusion complex, including UV-Visible, FT-IR, XRD, SEM, TGA, and DSC, which provided appropriate evidence to confirm the formation. A 1:1 stoichiometry was determined for B-CD:TFR inclu-sion complex in aqueous medium from UV-Visible absorption spectra by using the Benesi-Hildebrand method. Phase solubility studies proposed that B-CD enhanced the excellent solubility of TFR and the sta-bility constant was obtained at 863 +/- 32 M-1. Moreover, the molecular docking confirmed the experimen-tal results demonstrated the most desirable mode of TFR encapsulated into the B-CD nanocavity via hydrophobic interactions and possible hydrogen bonds. Moreover, TFR was validated in the B-CD:TFR inclusion complex as potential inhibitors against SARS-CoV-2 main protease (Mpro) receptors by using in silico methods. The enhanced solubility, stability, and antiviral activity against SARS-CoV-2 (MPro) sug-gest that B-CD:TFR inclusion complexes can be further used as feasible water-insoluble antiviral drug car-riers in viral disease infection. (c) 2023 Elsevier B.V. All rights reserved.