Browsing by Author "Berber, Burak"

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Citation - WoS: 14
A Comprehensive Drug Repurposing Study for Covid19 Treatment: Novel Putative Dihydroorotate Dehydrogenase Inhibitors Show Association To Serotonin-Dopamine Receptors
(Oxford Univ Press, 2021) Berber, Burak; Doluca, Osman
Dihydroorotate dehydrogenase (DHODH) is a key enzyme required for de novo pyrimidine synthesis and it is suggested as a target for COVID19 treatment due to high pyrimidine demand by the virus replication in the infected host cells as well as its proven effect of blocking of cytokine release by the immune cells to prevent inflammation leading to acute respiratory distress. There are a number of clinical trials underway for COVID19 treatment using DHODH inhibitors; however, there are only a small number of known DHODH antagonists available for testing. Here, we have applied a methodology to identify DHODH antagonist candidates, and compared them using in silico target prediction tools. A large set of 7900 FDA-approved and clinical stage drugs obtained from DrugBank were docked against 20 different structures DHODH available in PDB. Drugs were eliminated according to their predicted affinities by Autodock Vina. About 28 FDA-approved and 79 clinical trial ongoing drugs remained. The mode of interaction of these molecules was analyzed by repeating docking using Autodock 4 and DS Visualiser. Finally, the target region predictions of 28 FDA-approved drugs were determined through PASS and SwissTargetPrediction tools. Interestingly, the analysis of in silico target predictions revealed that serotonin-dopamine receptor antagonists could also be potential DHODH inhibitors. Our candidates shared a common attribute, a possible interaction with serotonin-dopamine receptors as well as other oxidoreductases, like DHODH. Moreover, the Bruton Tyrosine Kinase-inhibitor acalabrutunib and serotonin-dopamine receptor inhibitor drugs on our list have been found in the literature that have shown to be effective against Sars-CoV-2, while the path of activity is yet to be identified. Identifying an effective drug that can suppress both inflammation and virus proliferation will play a crucial role in the treatment of COVID. Therefore, we suggest experimental investigation of the 28 FDA-approved drugs on DHODH activity and Sars-CoV-2 virus proliferation. Those who are found experimentally effective can play an important role in COVID19 treatment. Moreover, we suggest investigating COVID19 case conditions in patients using schizophrenia and depression drugs.
Citation - WoS: 43
Citation - Scopus: 44
G-Quadruplex Prediction in E. Coli Genome Reveals a Conserved Putative G-Quadruplex Switch
(Oxford Univ Press, 2016) Kaplan, Oktay I.; Berber, Burak; Hekim, Nezih; Doluca, Osman
Many studies show that short non-coding sequences are widely conserved among regulatory elements. More and more conserved sequences are being discovered since the development of next generation sequencing technology. A common approach to identify conserved sequences with regulatory roles relies on topological changes such as hairpin formation at the DNA or RNA level. G-quadruplexes, non-canonical nucleic acid topologies with little established biological roles, are increasingly considered for conserved regulatory element discovery. Since the tertiary structure of G-quadruplexes is strongly dependent on the loop sequence which is disregarded by the generally accepted algorithm, we hypothesized that G-quadruplexes with similar topology and, indirectly, similar interaction patterns, can be determined using phylogenetic clustering based on differences in the loop sequences. Phylogenetic analysis of 52 G-quadruplex forming sequences in the Escherichia coli genome revealed two conserved G-quadruplex motifs with a potential regulatory role. Further analysis revealed that both motifs tend to form hairpins and G quadruplexes, as supported by circular dichroism studies. The phylogenetic analysis as described in this work can greatly improve the discovery of functional G-quadruplex structures and may explain unknown regulatory patterns.
Citation - WoS: 3
Citation - Scopus: 3
A Novel Method for Conserved Sequence Extraction With Prospective Mutation Prediction for Sars-Cov Pcr Primer Design
(Elsevier, 2021) Portakal, Saygin Huseyin; Kanat, Beyza; Sayan, Murat; Berber, Burak; Doluca, Osman
While the whole genomic sequence of SARS-CoV-2 had been revealed, it was also demonstrated that the genome of SARS-CoV-2 exhibits identity with the genome of SARS-CoV and MERS-CoV with ratios of 80 % and 50 % respectively. In the light of SARS-CoV-2 infection and mortality data, diagnosis and treatment of COVID-19 came into prominence around the world. As such many RT-PCR kits have been developed by biotechnology scientists. However viruses are fast mutating organisms and in order to increase accuracy, feasibility in long term and avoid the off target results of RT-PCR assays, regions of viral genome with low mutation rate and designing of primers targeting these regions are quite important. In this scope, we are presenting a novel algorithm that could be used for finding low mutation rate regions of SARS-CoV-2 and primers that were designed according to findings from our algorithm in this study.
Citation - WoS: 11
Citation - Scopus: 11
dna Binding Effects of 2,2'-bipyridine and 1,10-Phenanthroline Ligands Synthesized With Benzimidazole Copper (ii) Complexes: Crystal Structure, Molecular Docking, Dna Binding and Anti-Cancer Studies
(Pergamon-Elsevier Science Ltd, 2022) Unver, Hakan; Berber, Burak; Kanat, Beyza; Arafat, Mahmoud; Koparal, Ayse Tansu; Doluca, Osman
Two new copper(II) complexes, [Cu(benzim)2(bipy)(MeOH)](ClO4)(2) (Complex 1) and Cu(benzim)2(phen) (MeOH)](ClO4)(2) (Complex 2)] (bipy = 2,2'-bipyridine, phen = 1,10-phenanthroline and benzim = 1-benzyl-1Hbenzimidazole) have been synthesized and successfully characterized with single crystal x-ray diffraction analysis. Crystal structures of complexes revealed that both possess distorted square pyramidal geometries coordinated with a solvent molecule (CH3OH) at apical positions. The in vitro cytotoxicity of these Cu(II) complexes was carried out in HCC1428 and HUVEC cell lines. Molecular docking was also used to evaluate and understand the interaction modes of the complexes with the molecular target DNA and HSA (Human Serum Albumin). DNA binding capacities of complexes were analyzed by fluorescent titration method. Structural changes in the nucleus as a result of the effects of the complexes were discussed by viewing them with DAPI staining. Furthermore, biological activities of complexes and ligands were analyzed in silico. The cell lines IC50 results were obtained at similar rates (~8-fold) to the constant inhibition values obtained by docking studies. In addition, the fluorescence titration and circular dichrosim studies of the compounds with dsDNA-TO complexes showed results in agreement with docking studies. In our study, it was determined that phen ligand has a much more effective biological activity than bipy ligand in copper(II) complex synthesized with benzimidazole.