Interaction of certain monoterpenoid hydrocarbons with the receptor binding domain of 2019 novel coronavirus (2019-nCoV), transmembrane serine protease 2 (TMPRSS2), cathepsin B, and cathepsin L (CatB/L) and their pharmacokinetic properties

Authors : Erman Salih ISTİFLİ, Arzuhan Sihoglu TEPE, Cengiz SARİKURKCU, Bektas TEPE

Pages : 242-264

View : 13 | Download : 5

Publication Date : 2020-12-01

Article Type : Research Paper

Abstract :As of June 2020, the coronavirus disease 19 insert ignore into journalissuearticles values(COVID-19); caused by the 2019 new type coronavirus insert ignore into journalissuearticles values(2019-nCoV); infected more than 7,000,000 people worldwide and caused the death of more than 400,000 people. The aim of this study was to investigate the molecular interactions between monoterpenoids and spike protein of 2019-nCoV together with the cellular proteases [transmembrane serine protease 2 insert ignore into journalissuearticles values(TMPRSS2);, cathepsin B insert ignore into journalissuearticles values(CatB);, and cathepsin L insert ignore into journalissuearticles values(CatL);]. As a result of the relative binding capacity index insert ignore into journalissuearticles values(RBCI); analysis, carvone was found to be the most effective molecule against all targets when binding energy and predicted insert ignore into journalissuearticles values(theoretical); IC50 data were evaluated together. It was found to exhibit drug-likeness property according to the Lipinski’s rule-of-five. Carvone has also been determined to be able to cross the blood-brain barrier insert ignore into journalissuearticles values(BBB); effectively, not a substrate for P-glycoprotein insert ignore into journalissuearticles values(P-gp);, not to inhibit any of the cytochrome P molecules, and to have no toxic effects even on liver cells. In addition, the LD50 dose of carvone in rats was 1.707 mol/kg. Due to its interaction profile with target proteins and excellent pharmacokinetic properties, it has been concluded that carvone can be considered as an alternative agent in drug development studies against 2019-nCoV.
Keywords : 2019 nCoV, ACE2, TMPRSS2, cathepsin, monoterpene, docking, pharmacokinetic