Selected article for: "fusion protein and high affinity"
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_32
    Snippet: The authors have not filed for patent protection on the SARS-CoV-2 host interactions or the use of predicted drugs for treating COVID-19 to ensure all the information is freely available to accelerate the discovery of a treatment. The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.22.002386 doi: bioRxiv preprint similarity with the SARS-CoV homolog, and inferred function based on the SARS.....
    Document: The authors have not filed for patent protection on the SARS-CoV-2 host interactions or the use of predicted drugs for treating COVID-19 to ensure all the information is freely available to accelerate the discovery of a treatment. The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.22.002386 doi: bioRxiv preprint similarity with the SARS-CoV homolog, and inferred function based on the SARS-CoV homolog. (c) Immunoblot detection of 2xStrep tag demonstrates expression of each bait in input samples, as indicated by red arrowhead. (d) Experimental workflow for expressing each 2xStrep tagged SARS-CoV-2 fusion protein in biological triplicate in HEK293T cells, followed by affinity purification-mass spectrometry, and PPI scoring to identify 332 high confidence protein-protein interactions. The copyright holder for this preprint (which was not peer-reviewed) is the . https://doi.org/10.1101/2020.03.22.002386 doi: bioRxiv preprint transmembrane segment. (iii) Model of how E might mimic the BRD2 native interaction partner Histone 2A and how BRD2 can be targeted pharmacologically. Chemoinformatic and expert analysis identified FDA approved drugs (green), clinical candidates (yellow), and preclinical candidates (purple) with experimental activities against the host proteins and processes, with representative chemicals shown. (b) Inosine Monophosphate Dehydrogenase 2 (IMPDH2) regulates de novo nucleic acid biosynthesis. It is a target for proliferative diseases including cancer 81 and autoimmune disorders, for instance by the approved drug mycophenolic acid 82 , and as a broad spectrum antiviral by Ribavirin 83 . While Ribavirin has activity against SARS in vitro 84 , it has low tolerability, something that might be addressed by the more selective Merimepodib, which is in phase II clinical trials 85 . (c) The mammalian target of Rapamycin (mTOR) pathway is a master regulator of cell proliferation and autophagy, which viruses including Influenza A are known to modulate 86, 87 . Several proteins that interact with SARS-CoV-2 baits, including components of the Respiratory complex 1 by Nsp7, Nsp12, and Orf9c, the leucine importer B(0)AT2 (SLC6A15) 88,89 by Nsp6 and LARP1 by N (not shown). In addition to Rapamycin, the mTOR pathway can be indirectly modulated by metformin, a widely prescribed diabetes drug, and by Sapanisertib, a drug in clinical trials for solid tumors 61 .

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