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Near-physiological-temperature serial crystallography reveals conformations of SARS-CoV-2 main protease active site for improved drug repurposing.
Durdagi, Serdar; Dag, Çagdas; Dogan, Berna; Yigin, Merve; Avsar, Timucin; Buyukdag, Cengizhan; Erol, Ismail; Ertem, Fatma Betul; Calis, Seyma; Yildirim, Gunseli; Orhan, Muge D; Guven, Omur; Aksoydan, Busecan; Destan, Ebru; Sahin, Kader; Besler, Sabri O; Oktay, Lalehan; Shafiei, Alaleh; Tolu, Ilayda; Ayan, Esra; Yuksel, Busra; Peksen, Ayse B; Gocenler, Oktay; Yucel, Ali D; Can, Ozgur; Ozabrahamyan, Serena; Olkan, Alpsu; Erdemoglu, Ece; Aksit, Fulya; Tanisali, Gokhan; Yefanov, Oleksandr M; Barty, Anton; Tolstikova, Alexandra; Ketawala, Gihan K; Botha, Sabine; 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; DeMirci, Hasan.
  • Durdagi S; Computational Biology and Molecular Simulations Laboratory, Department of Biophysics, School of Medicine, Bahcesehir University, Istanbul 34734, Turkey. Electronic address: serdar.durdagi@bahcesehir.edu.tr.
  • Dag Ç; Department of Molecular Biology and Genetics, Koc University, Istanbul 34450, Turkey.
  • Dogan B; Computational Biology and Molecular Simulations Laboratory, Department of Biophysics, School of Medicine, Bahcesehir University, Istanbul 34734, Turkey.
  • Yigin M; Department of Molecular Biology and Genetics, Koc University, Istanbul 34450, Turkey.
  • Avsar T; Department of Medical Biology, School of Medicine, Bahcesehir University, Istanbul 34734, Turkey.
  • Buyukdag C; Department of Molecular Biology and Genetics, Koc University, Istanbul 34450, Turkey.
  • Erol I; Computational Biology and Molecular Simulations Laboratory, Department of Biophysics, School of Medicine, Bahcesehir University, Istanbul 34734, Turkey; Department of Chemistry, Gebze Technical University, Kocaeli 41400, Turkey.
  • Ertem FB; Department of Molecular Biology and Genetics, Koc University, Istanbul 34450, Turkey.
  • Calis S; Department of Medical Biology, School of Medicine, Bahcesehir University, Istanbul 34734, Turkey; Department of Molecular Biology - Genetics and Biotechnology, Istanbul Technical University, Istanbul 34469, Turkey.
  • Yildirim G; Department of Molecular Biology and Genetics, Koc University, Istanbul 34450, Turkey.
  • Orhan MD; Department of Medical Biology, School of Medicine, Bahcesehir University, Istanbul 34734, Turkey.
  • Guven O; Department of Molecular Biology and Genetics, Koc University, Istanbul 34450, Turkey.
  • Aksoydan B; Computational Biology and Molecular Simulations Laboratory, Department of Biophysics, School of Medicine, Bahcesehir University, Istanbul 34734, Turkey; Neuroscience Program, Graduate School of Health Sciences, Bahcesehir University, Istanbul 34734, Turkey.
  • Destan E; Department of Molecular Biology and Genetics, Koc University, Istanbul 34450, Turkey.
  • Sahin K; Computational Biology and Molecular Simulations Laboratory, Department of Biophysics, School of Medicine, Bahcesehir University, Istanbul 34734, Turkey.
  • Besler SO; Department of Molecular Biology and Genetics, Koc University, Istanbul 34450, Turkey.
  • Oktay L; Computational Biology and Molecular Simulations Laboratory, Department of Biophysics, School of Medicine, Bahcesehir University, Istanbul 34734, Turkey.
  • Shafiei A; Department of Molecular Biology and Genetics, Koc University, Istanbul 34450, Turkey.
  • Tolu I; Computational Biology and Molecular Simulations Laboratory, Department of Biophysics, School of Medicine, Bahcesehir University, Istanbul 34734, Turkey.
  • Ayan E; Department of Molecular Biology and Genetics, Koc University, Istanbul 34450, Turkey.
  • Yuksel B; Department of Molecular Biology and Genetics, Koc University, Istanbul 34450, Turkey.
  • Peksen AB; Department of Molecular Biology and Genetics, Koc University, Istanbul 34450, Turkey.
  • Gocenler O; Department of Molecular Biology and Genetics, Koc University, Istanbul 34450, Turkey.
  • Yucel AD; Department of Molecular Biology and Genetics, Koc University, Istanbul 34450, Turkey.
  • Can O; Department of Molecular Biology and Genetics, Koc University, Istanbul 34450, Turkey.
  • Ozabrahamyan S; Department of Molecular Biology and Genetics, Koc University, Istanbul 34450, Turkey.
  • Olkan A; Computational Biology and Molecular Simulations Laboratory, Department of Biophysics, School of Medicine, Bahcesehir University, Istanbul 34734, Turkey; School of Medicine, Bahcesehir University, Istanbul 34734, Turkey.
  • Erdemoglu E; Computational Biology and Molecular Simulations Laboratory, Department of Biophysics, School of Medicine, Bahcesehir University, Istanbul 34734, Turkey; Faculty of Medicine, Mersin University, Mersin 33070, Turkey.
  • Aksit F; Department of Molecular Biology and Genetics, Koc University, Istanbul 34450, Turkey.
  • Tanisali G; Department of Molecular Biology and Genetics, Koc University, Istanbul 34450, Turkey.
  • Yefanov OM; Deutsches Elektronen-Synchrotron, Notkestrasse 85, Hamburg 22607, Germany.
  • Barty A; Deutsches Elektronen-Synchrotron, Notkestrasse 85, Hamburg 22607, Germany.
  • Tolstikova A; Deutsches Elektronen-Synchrotron, Notkestrasse 85, Hamburg 22607, Germany.
  • Ketawala GK; Department of Physics, Arizona State University, Tempe, AZ 85287-1504, USA; Biodesign Center for Applied Structural Discovery, Arizona State University, Tempe, AZ 85287-5001, USA.
  • Botha S; Department of Physics, Arizona State University, Tempe, AZ 85287-1504, USA; Biodesign Center for Applied Structural Discovery, Arizona State University, Tempe, AZ 85287-5001, USA.
  • Dao EH; Stanford PULSE Institute, SLAC National Laboratory, Menlo Park, CA 94025, USA.
  • Hayes B; Linac Coherent Light Source, SLAC National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025, USA.
  • Liang M; Linac Coherent Light Source, SLAC National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025, USA.
  • Seaberg MH; Linac Coherent Light Source, SLAC National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025, USA.
  • Hunter MS; Linac Coherent Light Source, SLAC National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025, USA.
  • Batyuk A; Linac Coherent Light Source, SLAC National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025, USA.
  • Mariani V; Linac Coherent Light Source, SLAC National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025, USA.
  • Su Z; Linac Coherent Light Source, SLAC National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025, USA; Department of Applied Physics, Stanford University, Stanford, CA, USA.
  • Poitevin F; Linac Coherent Light Source, SLAC National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025, USA.
  • Yoon CH; Linac Coherent Light Source, SLAC National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025, USA.
  • Kupitz C; Linac Coherent Light Source, SLAC National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025, USA.
  • Sierra RG; Linac Coherent Light Source, SLAC National Accelerator Laboratory, 2575 Sand Hill Road, Menlo Park, CA 94025, USA.
  • Snell EH; Hauptman-Woodward Medical Research Institute, University at Buffalo, 700 Ellicott St, Buffalo, NY, USA; Materials Design and Innovation, SUNY at Buffalo, 700 Ellicott St., Buffalo, NY, USA.
  • DeMirci H; Department of Molecular Biology and Genetics, Koc University, Istanbul 34450, Turkey; Stanford PULSE Institute, SLAC National Laboratory, Menlo Park, CA 94025, USA; Koc University Isbank Center for Infectious Diseases (KUISCID), 34450, Istanbul, Turkey. Electronic address: hdemirci@ku.edu.tr.
Structure ; 29(12): 1382-1396.e6, 2021 12 02.
Article in English | MEDLINE | ID: covidwho-1356461
ABSTRACT
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.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: Drug Design / Drug Repositioning / Coronavirus 3C Proteases / SARS-CoV-2 / COVID-19 Drug Treatment Topics: Vaccines Language: English Journal: Structure Journal subject: Molecular Biology / Biochemistry / Biotechnology Year: 2021 Document Type: Article

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Full text: Available Collection: International databases Database: MEDLINE Main subject: Drug Design / Drug Repositioning / Coronavirus 3C Proteases / SARS-CoV-2 / COVID-19 Drug Treatment Topics: Vaccines Language: English Journal: Structure Journal subject: Molecular Biology / Biochemistry / Biotechnology Year: 2021 Document Type: Article