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Comprehensive Fragment Screening of the SARS-CoV-2 Proteome Explores Novel Chemical Space for Drug Development.
Berg, Hannes; Wirtz Martin, Maria A; Altincekic, Nadide; Alshamleh, Islam; Kaur Bains, Jasleen; Blechar, Julius; Ceylan, Betül; de Jesus, Vanessa; Dhamotharan, Karthikeyan; Fuks, Christin; Gande, Santosh L; Hargittay, Bruno; Hohmann, Katharina F; Hutchison, Marie T; Marianne Korn, Sophie; Krishnathas, Robin; Kutz, Felicitas; Linhard, Verena; Matzel, Tobias; Meiser, Nathalie; Niesteruk, Anna; Pyper, Dennis J; Schulte, Linda; Trucks, Sven; Azzaoui, Kamal; Blommers, Marcel J J; Gadiya, Yojana; Karki, Reagon; Zaliani, Andrea; Gribbon, Philip; da Silva Almeida, Marcius; Dinis Anobom, Cristiane; Bula, Anna L; Bütikofer, Matthias; Putinhon Caruso, Ícaro; Caterina Felli, Isabella; Da Poian, Andrea T; Cardoso de Amorim, Gisele; Fourkiotis, Nikolaos K; Gallo, Angelo; Ghosh, Dhiman; Gomes-Neto, Francisco; Gorbatyuk, Oksana; Hao, Bing; Kurauskas, Vilius; Lecoq, Lauriane; Li, Yunfeng; Cunha Mebus-Antunes, Nathane; Mompeán, Miguel; Cristtina Neves-Martins, Thais.
  • Berg H; Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt, 60438, Frankfurt am Main, Germany.
  • Wirtz Martin MA; Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt, Frankfurt am Main (Germany), Max-von-LaueStrasse 7+9, 60438, Frankfurt am Main, Germany.
  • Altincekic N; Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt, 60438, Frankfurt am Main, Germany.
  • Alshamleh I; Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt, Frankfurt am Main (Germany), Max-von-LaueStrasse 7+9, 60438, Frankfurt am Main, Germany.
  • Kaur Bains J; Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt, 60438, Frankfurt am Main, Germany.
  • Blechar J; Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt, Frankfurt am Main (Germany), Max-von-LaueStrasse 7+9, 60438, Frankfurt am Main, Germany.
  • Ceylan B; Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt, 60438, Frankfurt am Main, Germany.
  • de Jesus V; Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt, Frankfurt am Main (Germany), Max-von-LaueStrasse 7+9, 60438, Frankfurt am Main, Germany.
  • Dhamotharan K; Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt, 60438, Frankfurt am Main, Germany.
  • Fuks C; Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt, Frankfurt am Main (Germany), Max-von-LaueStrasse 7+9, 60438, Frankfurt am Main, Germany.
  • Gande SL; Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt, 60438, Frankfurt am Main, Germany.
  • Hargittay B; Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt, 60438, Frankfurt am Main, Germany.
  • Hohmann KF; Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt, Frankfurt am Main (Germany), Max-von-LaueStrasse 7+9, 60438, Frankfurt am Main, Germany.
  • Hutchison MT; Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt, 60438, Frankfurt am Main, Germany.
  • Marianne Korn S; Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt, Frankfurt am Main (Germany), Max-von-LaueStrasse 7+9, 60438, Frankfurt am Main, Germany.
  • Krishnathas R; Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt, Frankfurt am Main (Germany), Max-von-LaueStrasse 7+9, 60438, Frankfurt am Main, Germany.
  • Kutz F; Institute for Molecular Biosciences, Goethe University Frankfurt, Max-von-Laue Strasse 7+9, 60438, Frankfurt am Main, Germany.
  • Linhard V; Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt, 60438, Frankfurt am Main, Germany.
  • Matzel T; Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt, 60438, Frankfurt am Main, Germany.
  • Meiser N; Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt, Frankfurt am Main (Germany), Max-von-LaueStrasse 7+9, 60438, Frankfurt am Main, Germany.
  • Niesteruk A; Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt, 60438, Frankfurt am Main, Germany.
  • Pyper DJ; Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt, Frankfurt am Main (Germany), Max-von-LaueStrasse 7+9, 60438, Frankfurt am Main, Germany.
  • Schulte L; Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt, 60438, Frankfurt am Main, Germany.
  • Trucks S; Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt, Frankfurt am Main (Germany), Max-von-LaueStrasse 7+9, 60438, Frankfurt am Main, Germany.
  • Azzaoui K; Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt, 60438, Frankfurt am Main, Germany.
  • Blommers MJJ; Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt, Frankfurt am Main (Germany), Max-von-LaueStrasse 7+9, 60438, Frankfurt am Main, Germany.
  • Gadiya Y; Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt, Frankfurt am Main (Germany), Max-von-LaueStrasse 7+9, 60438, Frankfurt am Main, Germany.
  • Karki R; Institute for Molecular Biosciences, Goethe University Frankfurt, Max-von-Laue Strasse 7+9, 60438, Frankfurt am Main, Germany.
  • Zaliani A; Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt, 60438, Frankfurt am Main, Germany.
  • Gribbon P; Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt, Frankfurt am Main (Germany), Max-von-LaueStrasse 7+9, 60438, Frankfurt am Main, Germany.
  • da Silva Almeida M; Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt, 60438, Frankfurt am Main, Germany.
  • Dinis Anobom C; Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt, Frankfurt am Main (Germany), Max-von-LaueStrasse 7+9, 60438, Frankfurt am Main, Germany.
  • Bula AL; Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt, 60438, Frankfurt am Main, Germany.
  • Bütikofer M; Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt, Frankfurt am Main (Germany), Max-von-LaueStrasse 7+9, 60438, Frankfurt am Main, Germany.
  • Putinhon Caruso Í; Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt, 60438, Frankfurt am Main, Germany.
  • Caterina Felli I; Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt, Frankfurt am Main (Germany), Max-von-LaueStrasse 7+9, 60438, Frankfurt am Main, Germany.
  • Da Poian AT; Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt, 60438, Frankfurt am Main, Germany.
  • Cardoso de Amorim G; Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt, 60438, Frankfurt am Main, Germany.
  • Fourkiotis NK; Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt, Frankfurt am Main (Germany), Max-von-LaueStrasse 7+9, 60438, Frankfurt am Main, Germany.
  • Gallo A; Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt, 60438, Frankfurt am Main, Germany.
  • Ghosh D; Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt, Frankfurt am Main (Germany), Max-von-LaueStrasse 7+9, 60438, Frankfurt am Main, Germany.
  • Gomes-Neto F; Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt, 60438, Frankfurt am Main, Germany.
  • Gorbatyuk O; Center of Biomolecular Magnetic Resonance (BMRZ), Goethe University Frankfurt, Frankfurt am Main (Germany), Max-von-LaueStrasse 7+9, 60438, Frankfurt am Main, Germany.
  • Hao B; Institute for Organic Chemistry and Chemical Biology, Goethe University Frankfurt, 60438, Frankfurt am Main, Germany.
  • Kurauskas V; Saverna Therapeutics, Pumpmattenweg 3, 4105, Biel-Benken, Switzerland.
  • Lecoq L; Saverna Therapeutics, Pumpmattenweg 3, 4105, Biel-Benken, Switzerland.
  • Li Y; Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Screening Port, Schnackenburgallee 114, 22525, Hamburg, Germany.
  • Cunha Mebus-Antunes N; Fraunhofer Cluster of Excellence for Immune-Mediated Diseases (CIMD), Theodor-Stern-Kai 7, 60596, Frankfurt am Main, Germany.
  • Mompeán M; Fraunhofer Institute for Translational Medicine and Pharmacology (ITMP), Screening Port, Schnackenburgallee 114, 22525, Hamburg, Germany.
  • Cristtina Neves-Martins T; Fraunhofer Cluster of Excellence for Immune-Mediated Diseases (CIMD), Theodor-Stern-Kai 7, 60596, Frankfurt am Main, Germany.
Angew Chem Int Ed Engl ; 61(46): e202205858, 2022 Nov 14.
Article in English | MEDLINE | ID: covidwho-2034712
ABSTRACT
SARS-CoV-2 (SCoV2) and its variants of concern pose serious challenges to the public health. The variants increased challenges to vaccines, thus necessitating for development of new intervention strategies including anti-virals. Within the international Covid19-NMR consortium, we have identified binders targeting the RNA genome of SCoV2. We established protocols for the production and NMR characterization of more than 80 % of all SCoV2 proteins. Here, we performed an NMR screening using a fragment library for binding to 25 SCoV2 proteins and identified hits also against previously unexplored SCoV2 proteins. Computational mapping was used to predict binding sites and identify functional moieties (chemotypes) of the ligands occupying these pockets. Striking consensus was observed between NMR-detected binding sites of the main protease and the computational procedure. Our investigation provides novel structural and chemical space for structure-based drug design against the SCoV2 proteome.
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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Drug Treatment Type of study: Diagnostic study / Prognostic study Topics: Vaccines / Variants Limits: Humans Language: English Journal: Angew Chem Int Ed Engl Year: 2022 Document Type: Article Affiliation country: Anie.202205858

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Full text: Available Collection: International databases Database: MEDLINE Main subject: SARS-CoV-2 / COVID-19 Drug Treatment Type of study: Diagnostic study / Prognostic study Topics: Vaccines / Variants Limits: Humans Language: English Journal: Angew Chem Int Ed Engl Year: 2022 Document Type: Article Affiliation country: Anie.202205858