Selected article for: "investigation warrant and protein protein"
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_15
    Snippet: N targets stress granule protein G3BP1, an essential antiviral protein which is known to induce innate immune response through multiple mechanisms 52-54 . Common among coronaviridae is the manipulation of stress granules (SG) and related RNA biology, possibly leading to suppression of stress granules and host translation shutoff 55 . This functionality seems to benefit viral replication, as stress granules are inhibitory to replication of MERS-Co.....
    Document: N targets stress granule protein G3BP1, an essential antiviral protein which is known to induce innate immune response through multiple mechanisms 52-54 . Common among coronaviridae is the manipulation of stress granules (SG) and related RNA biology, possibly leading to suppression of stress granules and host translation shutoff 55 . This functionality seems to benefit viral replication, as stress granules are inhibitory to replication of MERS-CoV 56 and other viruses 57 . The SARS-CoV-2 nucleocapsid (N) interactome includes many host mRNA binding proteins, including the SG related factors G3BP1/2, the mTOR translational repressors LARP1, and the protein kinases CK2 (Fig. 4a ). SGs are induced by protein kinase R (PKR)-mediated phosphorylation of eIF2α upon viral dsRNA recognition 57 . Promoting G3BP aggregation via the eIF4A inhibitor Zotatafin 58,59 or reducing SG disassembly by Silmitasertib inhibition of CK2 60 warrant investigation for treatment of SARS-CoV-2. The mTOR inhibitor rapamycin disrupts the binding of LARP1 to mTORC1 61 and has been shown to reduce MERS infection by ~60% in vitro 62 , another drug that could be tested for repurposing.

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