Selected article for: "druggable target and small molecule"

Author: David E. Gordon; Gwendolyn M. Jang; Mehdi Bouhaddou; Jiewei Xu; Kirsten Obernier; Matthew J O'Meara; Jeffrey Z. Guo; Danielle L. Swaney; Tia A. Tummino; Ruth Huttenhain; Robyn Kaake; Alicia L. Richards; Beril Tutuncuoglu; Helene Foussard; Jyoti Batra; Kelsey Haas; Maya Modak; Minkyu Kim; Paige Haas; Benjamin J. Polacco; Hannes Braberg; Jacqueline M. Fabius; Manon Eckhardt; Margaret Soucheray; Melanie Brewer; Merve Cakir; Michael J. McGregor; Qiongyu Li; Zun Zar Chi Naing; Yuan Zhou; Shiming Peng; Ilsa T. Kirby; James E. Melnyk; John S Chorba; Kevin Lou; Shizhong A. Dai; Wenqi Shen; Ying Shi; Ziyang Zhang; Inigo Barrio-Hernandez; Danish Memon; Claudia Hernandez-Armenta; Christopher J.P. Mathy; Tina Perica; Kala B. Pilla; Sai J. Ganesan; Daniel J. Saltzberg; Rakesh Ramachandran; Xi Liu; Sara B. Rosenthal; Lorenzo Calviello; Srivats Venkataramanan; Yizhu Lin; Stephanie A. Wankowicz; Markus Bohn; Phillip P. Sharp; Raphael Trenker; Janet M. Young; Devin A. Cavero; Joseph Hiatt; Theo Roth; Ujjwal Rathore; Advait Subramanian; Julia Noack; Mathieu Hubert; Ferdinand Roesch; Thomas Vallet; Björn Meyer; Kris M. White; Lisa Miorin; Oren S. Rosenberg; Kliment A. Verba; David Agard; Melanie Ott; Michael Emerman; Davide Ruggero; Adolfo Garcí-Sastre; Natalia Jura; Mark von Zastrow; Jack Taunton; Olivier Schwartz; Marco Vignuzzi; Christophe d'Enfert; Shaeri Mukherjee; Matt Jacobson; Harmit S. Malik; Danica G Fujimori; Trey Ideker; Charles S Craik; Stephen Floor; James S. Fraser; John Gross; Andrej Sali; Tanja Kortemme; Pedro Beltrao; Kevan Shokat; Brian K. Shoichet; Nevan J. Krogan
Title: A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing
  • Document date: 2020_3_22
  • ID: 38d6gb7o_18
    Snippet: Viruses commonly hijack ubiquitination pathways for replication and pathogenesis 67 . The novel Orf10 of SARS-CoV-2 interacts with multiple members of a Cullin 2 (CUL2) RING E3 ligase complex (Fig. 4c) , specifically the CUL2 ZYG11B complex. ZYG11B, a substrate adapter of CUL2 that targets substrates with exposed N-terminal glycines for degradation 65 , is the highest scoring protein in the Orf10 interactome suggesting its direct interaction with.....
    Document: Viruses commonly hijack ubiquitination pathways for replication and pathogenesis 67 . The novel Orf10 of SARS-CoV-2 interacts with multiple members of a Cullin 2 (CUL2) RING E3 ligase complex (Fig. 4c) , specifically the CUL2 ZYG11B complex. ZYG11B, a substrate adapter of CUL2 that targets substrates with exposed N-terminal glycines for degradation 65 , is the highest scoring protein in the Orf10 interactome suggesting its direct interaction with Orf10. Orf10 may bind to the CUL2 ZYG11B complex and hijack it for ubiquitination and degradation of restriction factors. The ubiquitin transfer to a substrate requires neddylation of CUL2 via NEDD8-activating enzyme (NAE), a druggable target that can be inhibited by the small molecule Pevonedistat 68 (Fig. 4c ).

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