Busecan Aksoydan

% IMPORTANT: The following is UTF-8 encoded. This means that in the presence % of non-ASCII characters, it will not work with BibTeX or older. % Instead, you should use an up-to-date BibTeX implementation like “bibtex8” or % “biber”. @ARTICLE{Durdagi, author = {Durdagi, Serdar and Dağ, Çağdaş and Dogan, Berna and Yigin, Merve and Avsar, Timucin and Buyukdag, Cengizhan and Erol, Ismail and Ertem, Fatma Betul and Calis, Seyma and Yildirim, Gunseli and Orhan, Muge D. and Guven, Omur and Aksoydan, Busecan and Destan, Ebru and Sahin, Kader and Besler, Sabri O. and Oktay, Lalehan and Shafiei, Alaleh and Tolu, Ilayda and Ayan, Esra and Yuksel, Busra and Peksen, Ayse B. and Gocenler, Oktay and Yucel, Ali D. and Can, Ozgur and Ozabrahamyan, Serena and Olkan, Alpsu and Erdemoglu, Ece and Aksit, Fulya and Tanisali, Gokhan and Yefanov, Oleksandr M. and Barty, Anton and Tolstikova, Alexandra and Ketawala, Gihan K. and Botha, Sabine and Dao, E. Han and Hayes, Brandon and Liang, Mengning and Seaberg, Matthew H. and Hunter, Mark S. and Batyuk, Alex and Mariani, Valerio and Su, Zhen and Poitevin, Frederic and Yoon, Chun Hong and Kupitz, Christopher and Sierra, Raymond G. and Snell, Edward H. and DeMirci, Hasan}, title = {{N}ear-physiological-temperature serial crystallography reveals conformations of {SARS}-{C}o{V}-2 main protease active site for improved drug repurposing}, journal = {Structure}, volume = {29}, number = {12}, issn = {}, address = {Cambridge, Mass.}, publisher = {Cell Press}, reportid = {PUBDB}, pages = {e6}, year = {}, abstract = {The COVID pandemic has resulted in million reported infections and more than 4 million deaths as of July (funduszeue.info). Research to identify effective therapies for COVID includes: (1) designing a vaccine as future protection; (2) de novo drug discovery; and (3) identifying existing drugs to repurpose them as effective and immediate treatments. To assist in drug repurposing and design, we determine two apo structures of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) main protease at ambient temperature by serial femtosecond X-ray crystallography. We employ detailed molecular simulations of selected known main protease inhibitors with the structures and compare binding modes and energies. The combined structural and molecular modeling studies not only reveal the dynamics of small molecules targeting the main protease but also provide invaluable opportunities for drug repurposing and structure-based drug design strategies against SARS-CoV}, cin = {FS-CFEL-1 / FS-SC}, ddc = {}, cid = {I:(DE-H)FS-CFEL / I:(DE-H)FS-SC}, pnm = { - Life Sciences – Building Blocks of Life: Structure and Function (POF)}, pid = {G:(DE-HGF)POF}, experiment = {EXP:(DE-MLZ)External}, typ = {PUB:(DE-HGF)16}, pubmed = {pmid}, UT = {WOS}, doi = {/funduszeue.info}, url = {funduszeue.info}, }

Kitosan nano-parçacıkların pseudomonas aeruginosa üzerine antibakteriyel etkisinin ın silico ve ın vitro ortamlarda incelenmesi / The in silico and in vitro investigation of the antibacterial effect of chitosan nanoparticles on pseudomonas aeruginosa
Yazar:BUSECAN AKSOYDAN
Danışman: DOÇ. DR. FİGEN ESİN KAYHAN ; YRD. DOÇ. DR. NÜZHET CENK SESAL
Yer Bilgisi: Marmara Üniversitesi / Fen Bilimleri Enstitüsü / Biyoloji Ana Bilim Dalı
Konu:Biyoloji = Biology
Dizin:Pseudomonas aeruginosa = Pseudomonas aeruginosa Onaylandı
Yüksek Lisans
Türkçe

s.

Bakteriler, biyofilm formuna geçerek birçok tıbbi vakanın oluşmasına sebep olmaktadırlar. Fırsatçı patojenlerden Pseudomonas aeruginosa da biyofilm oluşturarak ciddi enfeksiyonlara sebep olabilmektedir. P. aeruginosa'nın biyofilm oluşturmasında rol oynayan Quorum Sensing (QS) mekanizmasının aydınlatılması yeni ilaçların geliştirilmesine öncülük edebilecektir. İlaç geliştirmede uygun hedefin belirlenmesi önem taşımaktadır. Son yıllarda uygun hedef bölgenin belirlenmesinde in silico çalışmalar ön plana çıkmaktadır. In silico yöntemler ile ilaç moleküllerinin in vivo ya da in vitro olarak test edilmesi için harcanan zamandan ve maliyetten tasarruf sağlanması beklenmektedir. Bu bilgiler ışığında P. aeruginosa PAO1 suşunda antimikrobiyal etkinliği bilinen kitosan ve kitosan nanoparçacıklarının antibakteriyel ve anti-QS etkisinin in silico ve in vitro ortamlarda incelenmesi amaçlanmıştır. Bu amaçla P. aeruginosa PAO1 suşunun QS ve ikili bileşen sistemine ait proteinlerinin üç boyutlu yapıları ile kitosan ve kitosan nanoparçacık moleküllerinin üç boyutlu yapıları çeşitli veri bankalarından elde edilerek moleküler kenetlenme işlemine tabi tutulmuştur. Bununla birlikte kitosanın ve kitosan nanoparçacıkların in vitro olarak P. aeruginosa PAO1 suşu üzerinde antibakteriyel ve anti-QS etkileri incelenmiştir. QS mekanizmasına ait proteinlerle gerçekleştirilen in silico işlemler sonucunda, kitosan molekülleri kitosan nanoparçacık molekülüne göre daha iyi skor vermiştir. Antibakteriyel aktivitede etkili proteinlerde ise kitosan nanoparçacık molekülü, kitosan moleküllerine göre daha iyi skor vermiştir. In vitro deneylerde uygulanan düşük dozda kitosan ve kitosan nanoparçacık çözeltilerinin P. aeruginosa PAO1 suşu üzerinde antibakteriyel veya anti-QS etkisine rastlanılmamışken, yüksek dozda uygulanan çözeltilerde sırasıyla HMW > MMW > Kitosan > LMW olarak antimikrobiyal aktivite gözlenmiştir. Sonuç olarak, in silico uygulamalarda kullanılan moleküllerin stabilitesi, boyutları, programların algoritmaları arasındaki farklılıklar gibi etmenlerin in vitro şartlarla uyum sağladığı durumlarda, in silico verilerle in vitro verilerin birbirini destekleyebileceği görülmüştür. Temmuz / Busecan AKSOYDAN

Bacteria may cause many different medical circumstances through their biofilm forms. Pseudomonas aeruginosa, one of the opportunistic pathogens, causes serious infections via biofilm formation as well. Elucidation of the Quorum Sensing (QS) mechanism, which plays a role in biofilm formation of P. aeruginosa, will be able to lead the development of new drugs. Determination of the appropriate target is carry weight in the developement of new drugs. Recently, in silico methods and studies have come into prominence for determination of the appropriate targets. In silico methods are expected to provide saving the cost and the time spent on testing the drug molecule candidates in vitro and in vivo. In the light of this information, the aim of our study is to investigate the antibacterial and anti-QS effects of the chitosan and chitosan nanoparticles, which are known for their antimicrobial effects, both in silico and in vitro on Pseudomonas aeruginosa PAO1 strain. The 3D structures of chitosan, chitosan nanoparticles and the proteins of P. aeruginosa PAO1 Quorum Sensing and Two Component System were downloaded from several databases, and several molecular docking studies were performed to this end. In addition, the antibacterial and anti-QS activities of chitosan and chitosan nanoparticles on P. aeruginosa PAO1 strain were investigated in vitro. The in silico results showed that chitosan molecules had better scores than chitosan nanoparticles on the proteins that play a role in QS mechanism. On the other hand, the chitosan nanoparticles had a better score than chitosan molecules on the proteins that are relevant to the antibacterial activity. As a result of in vitro experiments, neither antibacterial nor anti-QS effects on funduszeue.infonosa PAO1 strain were observed on the lower doses of chitosan and chitosan nanoparticles solutions, but we observed antimicrobial activities on the higher doses of HMW, MMW, Chitosan, LMW solutions, respectively. In conclusion, it seems possible that in silico and in vitro data could support each other under the appropriate conditions of adapted factors such as stability, size and dimension of the molecules in addition to the differences between the algorithms of programs used for in silico methods. July / Busecan AKSOYDAN

RESUMO

Small molecule inhibitors have previously been investigated in different studies as possible therapeutics in the treatment of SARS-CoV In the current drug repurposing study, we identified the leukotriene (D4) receptor antagonist Montelukast as a novel agent that simultaneously targets two important drug targets of SARS-CoV We initially demonstrated the dual inhibition profile of Montelukast through multiscale molecular modeling studies. Next, we characterized its effect on both targets by different in vitro experiments including the Fluorescent Resonance Energy Transfer (FRET)-based main protease enzyme inhibition assay, surface plasmon resonance (SPR) spectroscopy, pseudovirus neutralization on HEKT / hACE2, and virus neutralization assay using xCELLigence MP real time cell analyzer. Our integrated in silico and in vitro results confirmed the dual potential effect of the Montelukast both on virus entry into the host cell (Spike/ACE2) and on the main protease enzyme inhibition. The virus neutralization assay results showed that while no cytotoxicity of the Montelukast was observed at 12 μM concentration, the cell index time 50 (CIT 50 ) value was delayed for 12 hours. Moreover, it was also shown that Favipiravir, a well-known antiviral used in COVID therapy, should be used by fold higher concentrations than Montelukast in order to have the same effect of Montelukast. The rapid use of new small molecules in the pandemic is very important today. Montelukast, whose pharmacokinetic and pharmacodynamic properties are very well characterized and has been widely used in the treatment of asthma since , should urgently be completed in clinical phase studies and if its effect is proven in clinical phase studies, it should be used against COVID

Assuntos

COVID