Near-physiological-temperature serial crystallography reveals conformations of SARS-CoV-2 main protease active site for improved drug repurposing
| العنوان: | Near-physiological-temperature serial crystallography reveals conformations of SARS-CoV-2 main protease active site for improved drug repurposing |
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| المؤلفون: | Gunseli Yildirim, Alaleh Shafiei, Oleksandr Yefanov, Hasan DeMirci, Frédéric Poitevin, Timucin Avsar, Chun Hong Yoon, Muge Didem Orhan, Merve Yigin, Lalehan Oktay, Fulya Aksit, Çağdaş Dağ, Serdar Durdagi, Christopher Kupitz, Omur Guven, Valerio Mariani, Ece Erdemoglu, Ebru Destan, Edward H. Snell, Ismail Erol, Mark S. Hunter, Esra Ayan, Berna Dogan, Mengning Liang, Busecan Aksoydan, A. Batyuk, Ozgur Can, Cengizhan Buyukdag, Sabri O. Besler, Seyma Calis, Brandon Hayes, Matthew Seaberg, Serena Ozabrahamyan, Ilayda Tolu, Gihan K. Ketawala, Anton Barty, Raymond G. Sierra, Kader Sahin, Gokhan Tanisali, Oktay Gocenler, Ali D. Yucel, E. Han Dao, Alpsu Olkan, Ayse B. Peksen, Zhen Su, A. Tolstikova, Sabine Botha, Busra Yuksel, Fatma Betul Ertem |
| المساهمون: | Demirci, Hasan (ORCID 0000-0002-9135-5397 & YÖK ID 307350), Dağ, Çağdaş, Yığın, Merve, Büyükdağ, Cengizhan, Ertem, Fatma Betül, Yıldırım, Günseli, Destan, Ebru, Güven, Ömür, Ayan, Esra, Yüksel, Büşra, Pekşen, Ayşe Buket, Göçenler, Oktay, Yücel, Ali Doğa, Can, Özgür, Ozabrahamyan, Serena, Shafiei, Alaleh, Akşit, Fulya, Tanısalı, Gökhan, Besler, Sabri Özkan, Durdağı, Serdar, Doğan, Berna, Avşar, Timuçin, Erol, İsmail, Çalış, Şeyma, Orhan, Müge D., Aksoydan, Busecan, Şahin, Kader, Oktay, Lalehan, Tolu, İlayda, Olkan, Alpsu, Erdemoğlu, Ece, Yefanov, Oleksandr M., Dao, E. Han, Hayes, Brandon, Liang, Mengning, Seaberg, Matthew H., Hunter, Mark S., Batyuk, Alex, Mariani, Valerio, Su, Zhen, Poitevin, Frederic, Yoon, Chun Hong, Kupitz, Christopher, Sierra, Raymond G., Snell, Edward H., Koç Üniversitesi İş Bankası Enfeksiyon Hastalıkları Uygulama ve Araştırma Merkezi (EHAM) / Koç University İşbank Center for Infectious Diseases (KU-IS CID), College of Sciences, Graduate School of Sciences and Engineering, School of Nursing, Department of Molecular Biology and Genetics, Department of Chemical and Biological Engineering, Department of Materials Science and Engineering |
| المصدر: | Structure 29(12), 1382-1396.e6 (2021). doi:10.1016/j.str.2021.07.007 Structure Structure (London, England : 1993) |
| بيانات النشر: | Cell Press, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Drug, Molecular model, Protein Conformation, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), media_common.quotation_subject, medicine.medical_treatment, ambient temperature, Molecular Conformation, Crystallography, X-Ray, Article, Structural Biology, Catalytic Domain, medicine, SFX, Computer Simulation, Molecular Biology, Coronavirus 3C Proteases, media_common, Principal Component Analysis, Protease, Biochemistry and molecular biology, Biophysics, Cell biology, biology, drug repurposing, Drug discovery, SARS-CoV-2, Drug Repositioning, Temperature, Active site, Small molecule, Recombinant Proteins, COVID-19 Drug Treatment, Molecular Docking Simulation, Drug repositioning, Crystallography, main protease, Drug Design, ddc:540, biology.protein, Dimerization, Ambient temperature, Drug repurposing, Main protease |
| الوصف: | The COVID-19 pandemic has resulted in 198 million reported infections and more than 4 million deaths as of July 2021 (covid19.who.int). Research to identify effective therapies for COVID-19 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-2. Graphical abstract Durdağı et al. represent radiation damage-free high-resolution SARS-CoV-2 main protease SFX structures obtained at near-physiological temperature and performed MD simulation of apo-form proteins and three known main protease inhibitors. The structures reveal alternate conformation, while MD simulation indicates asymmetric behavior of the protein, which is invaluable information for immediate drug-repurposing studies. |
| وصف الملف: | text/academic publication |
| اللغة: | English |
| URL الوصول: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::392e9ce96ee7ee4a53bb651f21b45fef https://bib-pubdb1.desy.de/record/462438 |
| حقوق: | OPEN |
| رقم الأكسشن: | edsair.doi.dedup.....392e9ce96ee7ee4a53bb651f21b45fef |
| قاعدة البيانات: | OpenAIRE |
| الوصف غير متاح. |