Studies of quantum mechanics/molecular docking on zanubrutinib as potential repurposed against Covid-19

Abstract

ABSTRACT. Recently, Zanubrutinib, as a novel, selective covalent and potent inhibitor Bruton’s tyrosine kinase (BTK), has been used to treat COVID-19 patients. In this regard, the interaction of Zanubrutinib with Bruton’s tyrosine kinase (BTK) inhibitor studied. The docking molecular and ONIOM2 (B3LYP/6-311G: UFF) methods were conducted to investigate the binding properties of Zanubrutinib with Bruton’s tyrosine kinase (BTK) inhibitor. The active sites of the Bruton’s tyrosine kinase (BTK) inhibitor is evaluated by docking molecular and is used for ONIOM2 calculations. The binding between Zanubrutinib and the BTK receptor is strong because values of the free binding energy are negative. The hydrogen bonds are formed between Zanubrutinib and three residues of the active amino acids Asn484, Arg 525, and Asn 526 at 2.69, 3.15, and 2.75 Å, respectively, which create through the O-atom, and the N-atom of Zanubrutinib. ONIOM2 calculation was displayed that the stability system in the solvent phase is higher than the gas-phase, which can occur due to the solvation of the species. Our results display the first mechanistic study of BTK inactivation by Zanubrutinib. This study can be helpful in the design of covalent drugs that target BTK and other similar targets.                   KEY WORDS: Bruton’s tyrosine kinase inhibitor, Docking molecular, Zanubrutinib, Two-layer integrated orbital molecular mechanics   Bull. Chem. Soc. Ethiop. 2022, 36(2), 479-485.                                                              DOI: https://dx.doi.org/10.4314/bcse.v36i2.19