Temel Eczacılık Bilimleri Bölümühttps://hdl.handle.net/20.500.12933/1322024-03-28T13:11:12Z2024-03-28T13:11:12ZUnderstanding the molecular interaction of SARS-CoV-2 spike mutants with ACE2 (angiotensin converting enzyme 2)İstifli, Erman SalihNetz, Paulo A.Şıhoğlu Tepe, ArzuhanSarıkürkçü, CengizTepe, Bektaşhttps://hdl.handle.net/20.500.12933/8532022-04-28T08:42:38Z0008-01-01T00:00:00ZUnderstanding the molecular interaction of SARS-CoV-2 spike mutants with ACE2 (angiotensin converting enzyme 2)
İstifli, Erman Salih; Netz, Paulo A.; Şıhoğlu Tepe, Arzuhan; Sarıkürkçü, Cengiz; Tepe, Bektaş
Covid-19 is a viral disease caused by the virus SARS-CoV-2 that spread worldwide and caused more
than 4.3 million deaths. Moreover, SARS-CoV-2 still continues to evolve, and specifically the E484K,
N501Y, and South Africa triple (K417N þ E484K þ N501Y) spike protein mutants remain as the ‘escape’
phenotypes. The aim of this study was to compare the interaction between the receptor binding
domain (RBD) of the E484K, N501Y and South Africa triple spike variants and ACE2 with the interaction
between wild-type spike RBD-ACE2 and to show whether the obtained binding affinities and conformations corraborate clinical findings. The structures of the RBDs of the E484K, N501Y and South Africa
triple variants were generated with DS Studio v16 and energetically minimized using the CHARMM22
force field. Protein-protein dockings were performed in the HADDOCK server and the obtained wildtype and mutant spike-ACE2 complexes were submitted to 200-ns molecular dynamics simulations
with subsequent free energy calculations using GROMACS. Based on docking binding affinities and
free energy calculations the E484K, N501Y and triple mutant variants were found to interact stronger
with the ACE2 than the wild-type spike. Interestingly, molecular dynamics and MM-PBSA results
showed that E484K and spike triple mutant complexes were more stable than the N501Y one.
Moreover, the E484K and South Africa triple mutants triggered greater conformational changes in the
spike glycoprotein than N501Y. The E484K variant alone, or the combination of
K417N þ E484K þ N501Y mutations induce significant conformational transitions in the spike glycoprotein, while increasing the spike-ACE2 binding affinity
0008-01-01T00:00:00ZCytotoxic and genotoxic evaluation of copper oxychloride through Allium test and molecular docking studiesLiman, RecepAli, Muhammad MuddassirCiğerci, İbrahim Hakkıİstifli, Erman SalihSarıkürkçü, Cengizhttps://hdl.handle.net/20.500.12933/8412022-04-27T07:58:48Z0015-01-01T00:00:00ZCytotoxic and genotoxic evaluation of copper oxychloride through Allium test and molecular docking studies
Liman, Recep; Ali, Muhammad Muddassir; Ciğerci, İbrahim Hakkı; İstifli, Erman Salih; Sarıkürkçü, Cengiz
Copper oxychloride gained great importance due to its broad-spectrum antifungal action to combat various fungal diseases of plants. However, excess quantity of cupric fungicides on plants causes enzymatic changes and toxic effects. Thus, the current study was aimed to investigate the cytotoxicity and genotoxicity of copper oxychloride on Allium cepa root cells. The root growth, mitotic index (MI), chromosomal aberrations (CAs), and DNA damage were assessed through root growth inhibition, A. cepa ana-telophase, and alkaline comet assays. Furthermore, molecular docking was performed to evaluate binding affinities of two copper oxychloride polymorphs (atacamite and paratacamite) on DNA. In root growth inhibition test, onion root length was statistically significantly decreased by changing the copper oxychloride concentration from lower (2.64±0.11 cm) to higher (0.92±0.12 cm). Concentration- and time-dependent decrease in MI was observed whereas increase in CAs such as disturbed anatelophase, chromosome laggards, stickiness, anaphase bridges, and DNA damage were caused by the copper oxychloride on A. cepa root cells. Molecular docking results revealed that the two main polymorphs of copper oxychloride (atacamite and paratacamite) bind selectively to G and C nucleotides on the B-DNA structure. It is concluded that the atacamite- and paratacamite-induced DNA damage may be through minor groove recognition and intercalation. Findings of the current study revealed the cytotoxic and genotoxic effects of copper oxychloride on A. cepa root cells. However, further studies should be carried out at the molecular level to reveal the cyto-genotoxic mechanism of action of copper oxychloride in detail.
0015-01-01T00:00:00ZPhytochemical Composition, Antioxidant, and Enzyme Inhibition Activities of Methanolic Extracts of Two Endemic Onosma SpeciesKandasamy, SaravanakumarSarıkürkçü, CengizŞahinler, Saliha ŞeymaSarıkürkçü, Rabia BüşraWang, Myeong-Hyeonhttps://hdl.handle.net/20.500.12933/8372022-04-26T14:00:47Z0005-01-01T00:00:00ZPhytochemical Composition, Antioxidant, and Enzyme Inhibition Activities of Methanolic Extracts of Two Endemic Onosma Species
Kandasamy, Saravanakumar; Sarıkürkçü, Cengiz; Şahinler, Saliha Şeyma; Sarıkürkçü, Rabia Büşra; Wang, Myeong-Hyeon
Onosma species have been used as a dye for hundreds of years due to their dark red
pigments. These species have also been used by mankind in the treatment of various diseases since
ancient times. This work analyzed the phytochemical composition in methanol extract of two endemic
Onosma species (O. lycaonica and O. papillosa). Methanolic extract of these species varied in the content
of flavonoids and phenolics. The flavonoids were found higher in O. papillosa [32.9 ± 0.3 mg QEs
(quercetin equivalent)/g extracts] while the phenolics were higher in O. lycaonica [43.5 ± 1.5 mg
GAEs (gallic acid equivalent)/g extracts]. ESI-MS/MS (electrospray ionization-mass spectrometry)
revealed the presence of 25 compounds in O. lycaonica and 24 compounds in O. papillosa. The
former was richer than the latter for apigenin, luteolin, eriodictyol, pinoresinol, apigenin 7-glucoside,
rosmarinic acid, luteolin 7-glucoside, ferulic acid, vanillin, caffeic acid, 4-hydroxybenzoic acid, (+)-
catechin3,4-dihydroxyphenylacetic acid. The O. papillosa exhibited low EC50 (1.90 ± 0.07 mg/mL)
which indicated its strong phosphomolybdenum scavenging activity as compared to O. lycaonica.
However, the O. lycaonica showed low IC50 or EC50 for 1,1-diphenyl-2-picrylhydrazyl (DPPH),
2,20 -azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS+), cupric reducing antioxidant power
(CUPRAC), ferric reducing antioxidant power (FRAP) and ferrous ion chelating activity, as compared
to O. papillosa. The results proved the presence of potent antioxidant compounds in O. lycaonica.
Further, the plant extracts significantly varied for enzyme inhibition of acetylcholinesterase (AChE)
and butyrylcholinesterase (BChE), but the plant extracts did not significantly differ for inhibition of αglucosidase, α-amylase, and tyrosinase. Onosma species deserve further research towards developing
novel drugs to treat oxidative diseases.
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