Maria Beihaghi; Shima Ghasemi; Mohammad Reza Beihaghi; Nazanin Ataee; Mahsa Zabetian; Hanieh Hadizadeh
Abstract
Cytochromes are enzymes of the dehydrogenase class with a hemoprotein structure in which the iron in these compounds undergoes oxidation and reduction reactions upon receiving or losing electrons. Quantitatively speaking, CYP3A4 is the most important isoenzyme of cytochrome P450, oxidizing foreign organic ...
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Cytochromes are enzymes of the dehydrogenase class with a hemoprotein structure in which the iron in these compounds undergoes oxidation and reduction reactions upon receiving or losing electrons. Quantitatively speaking, CYP3A4 is the most important isoenzyme of cytochrome P450, oxidizing foreign organic molecules such as drugs or toxins to cause them to leave the body. Many drugs and antibiotics can induce or inhibit the activity of cytochrome P450, including dexamethasone. Dexamethasone is a steroidal anti-inflammatory drug used to treat of inflammatory diseases and chronic autoimmunity. This study aimed to investigate the induction effect of dexamethasone in biotransformation pathways by in silico tools. Molegro Virtual Docker software was used to investigate the molecular docking of the enzyme and dexamethasone, which indicated the binding of the drug to the enzyme. The molecular simulation was performed in Linux with the GROMACS program. Root-mean-square distance (RMSD), and radius of gyration (Rg), were evaluated. The results were analyzed with Pymol and VMD software, and the obtained curve was plotted with GRACE software. Docking results show that a cluster with a bond energy of -60.81 was the best cluster, and the bond size between ligand and internal atoms was -23.191in the complex. In addition, the amount of bond between the ligand and water for this pose was zero. The stability of the enzyme-ligand complex and the induction effect of dexamethasone on CYP3A4 were indicated by RMSD and RG results. Results of RMSD and RG of CYP3A4 glucocorticoid obtained from the simulation showed the stability of binding of the drug to the enzyme. Also, RMSD results showed the stability of glucocorticoid and dexamethasone complex during molecular dynamics simulation. It reached relative stability at 0.8 nm after 80,000 ps until the end of the simulation.
Mohammad Amin Manavi
Abstract
Coronavirus disease 2019 (COVID-19) has emerged in Wuhan, China, and because of fast transmission, it has led to its extensive prevalence in almost all countries, which has made it a global crisis. Drug repurposing is considered a fast way to discover new applications of the current drugs. This study ...
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Coronavirus disease 2019 (COVID-19) has emerged in Wuhan, China, and because of fast transmission, it has led to its extensive prevalence in almost all countries, which has made it a global crisis. Drug repurposing is considered a fast way to discover new applications of the current drugs. This study aims to recognize a possible small molecule as a primary protease inhibitor versus the main protease protein of SARS-CoV-2 by computational programs. Virtual screening procedures like using Molegro Virtual Docker, AutoDock Tool, and AutoDock Vina, were done for more than 1600 FDA-approved medicines downloaded from the ZINC database, were employed to characterize new implied molecule inhibitors for the recently published crystal structure of the main protease protein of SARS-CoV-2. Virtual screening results indicated, many drugs including ARBs, cephalosporins, some kinase inhibitors, HMG CoA reductase, and leukotriene receptor antagonist, may inhibit the main protease of SARS-COV-2. Velpatasvir, Molnupiravir, and Ivermectin were selected by virtual screening methods for further studies to find an efficient ligand for the treatment of COVID-19. Due to some other beneficial features, including anti-infectious, anti-inflammatory properties, and ADME profile, they could be a promising drug nominee for repurposing to the treatment of COVID-19. Velpatasvir was selected by some virtual screening methods for further studies to find a suitable ligand for the treatment of COVID-19. Furthermore, more studies need to approve this data and finally clinical trial needs to be done to examine the efficacy of Velpatasvir for the treatment of covid-19 as an anti-viral agent.
Salimeh Raeisi
Abstract
Monoamine oxidase (EC, 1.4.3.4) or amine oxidoreductase catalyzes the oxidative deamination of biogenic amines. Abnormal action of the monoamine oxidase B has been associated with neurological dysfunctions including parkinson´s disorder. Monoamine oxidase B inhibitors divulged that these agents were ...
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Monoamine oxidase (EC, 1.4.3.4) or amine oxidoreductase catalyzes the oxidative deamination of biogenic amines. Abnormal action of the monoamine oxidase B has been associated with neurological dysfunctions including parkinson´s disorder. Monoamine oxidase B inhibitors divulged that these agents were effective in the therapeutic management of Parkinson's disease. Understanding the interaction of monoamine oxidase binding site with inhibitors is crucial for the development of pharmaceutical agents. At the molecular docking, the exact prediction of the binding modes between the inhibitors and protein is of central importance in structure-based drug design. In the current study, we examined two classes of monoamine oxidase B inhibitors. We applied Autodock tools 4.2, in order to set up the docking runs and predict the inhibitors binding free energy. The final product of molecular docking was clustered to specify the binding free energy and optimal docking energy conformation that is investigated as the best docked structure. Docking results indicate that the contribution of van der Waals interactions is greater than electrostatic interactions so that, it can be concluded that all of the inhibitors attached to a hydrophobic binding site in monoamine oxidase B. Among the total of molecules tested, it was proved that 2-(2-cycloheptylidenehydrazinyl)-4-(2,4-dichlorophenyl)-1,3-thiazole has the lowest binding free energy and the lowest Van der Waals energy and also the lowest inhibition constant and subsequently the most experimental affinity. As well as, we find out a possible relationship between the estimated results and experimental data. The selective information from this work is crucial for the rational drug design of more potent and selective monoamine oxidase B inhibitors based on the 8-benzyloxycaffeine scaffold.
