Supplementary Materials

Comparative host-coronavirus protein interaction networks reveal panviral disease mechanisms

David E. Gordon, Joseph Hiatt, Mehdi Bouhaddou, Veronica V. Rezelj, Svenja Ulferts, Hannes Braberg, Alexander S. Jureka, Kirsten Obernier, Jeffrey Z. Guo, Jyoti Batra, Robyn M. Kaake, Andrew R. Weckstein, Tristan W. Owens, Meghna Gupta, Sergei Pourmal, Erron W. Titus, Merve Cakir, Margaret Soucheray, Michael McGregor, Zeynep Cakir, Gwendolyn Jang, Matthew J. O’Meara, Tia A. Tummino, Ziyang Zhang, Helene Foussard, Ajda Rojc, Yuan Zhou, Dmitry Kuchenov, Ruth Hüttenhain, Jiewei Xu, Manon Eckhardt, Danielle L. Swaney, Jacqueline M. Fabius, Manisha Ummadi, Beril Tutuncuoglu, Ujjwal Rathore, Maya Modak, Paige Haas, Kelsey M. Haas, Zun Zar Chi Naing, Ernst H. Pulido, Ying Shi, Inigo Barrio-Hernandez, Danish Memon, Eirini Petsalaki, Alistair Dunham, Miguel Correa Marrero, David Burke, Cassandra Koh, Thomas Vallet, Jesus A. Silvas, Caleigh M. Azumaya, Christian Billesbølle, Axel F. Brilot, Melody G. Campbell, Amy Diallo, Miles Sasha Dickinson, Devan Diwanji, Nadia Herrera, Nick Hoppe, Huong T. Kratochvil, Yanxin Liu, Gregory E. Merz, Michelle Moritz, Henry C. Nguyen, Carlos Nowotny, Cristina Puchades, Alexandrea N. Rizo, Ursula Schulze-Gahmen, Amber M. Smith, Ming Sun, Iris D. Young, Jianhua Zhao, Daniel Asarnow, Justin Biel, Alisa Bowen, Julian R. Braxton, Jen Chen, Cynthia M. Chio, Un Seng Chio, Ishan Deshpande, Loan Doan, Bryan Faust, Sebastian Flores, Mingliang Jin, Kate Kim, Victor L. Lam, Fei Li, Junrui Li, Yen-Li Li, Yang Li, Xi Liu, Megan Lo, Kyle E. Lopez, Arthur A. Melo, Frank R. Moss III, Phuong Nguyen, Joana Paulino, Komal Ishwar Pawar, Jessica K. Peters, Thomas H. Pospiech Jr., Maliheh Safari, Smriti Sangwan, Kaitlin Schaefer, Paul V. Thomas, Aye C. Thwin, Raphael Trenker, Eric Tse, Tsz Kin Martin Tsui, Feng Wang, Natalie Whitis, Zanlin Yu, Kaihua Zhang, Yang Zhang, Fengbo Zhou, Daniel Saltzberg, QCRG Structural Biology Consortium†, Anthony J. Hodder, Amber S. Shun-Shion, Daniel M. Williams, Kris M. White, Romel Rosales, Thomas Kehrer, Lisa Miorin, Elena Moreno, Arvind H. Patel, Suzannah Rihn, Mir M. Khalid, Albert Vallejo-Gracia, Parinaz Fozouni, Camille R. Simoneau, Theodore L. Roth, David Wu, Mohd Anisul Karim, Maya Ghoussaini, Ian Dunham, Francesco Berardi, Sebastian Weigang, Maxime Chazal, Jisoo Park, James Logue, Marisa McGrath, Stuart Weston, Robert Haupt, C. James Hastie, Matthew Elliott, Fiona Brown, Kerry A. Burness, Elaine Reid, Mark Dorward, Clare Johnson, Stuart G. Wilkinson, Anna Geyer, Daniel M. Giesel, Carla Baillie, Samantha Raggett, Hannah Leech, Rachel Toth, Nicola Goodman, Kathleen C. Keough, Abigail L. Lind, Zoonomia Consortium‡, Reyna J. Klesh, Kafi R. Hemphill, Jared Carlson-Stevermer, Jennifer Oki, Kevin Holden, Travis Maures, Katherine S. Pollard, Andrej Sali, David A. Agard, Yifan Cheng, James S. Fraser, Adam Frost, Natalia Jura, Tanja Kortemme, Aashish Manglik, Daniel R. Southworth, Robert M. Stroud, Dario R. Alessi, Paul Davies, Matthew B. Frieman, Trey Ideker, Carmen Abate, Nolwenn Jouvenet, Georg Kochs, Brian Shoichet, Melanie Ott, Massimo Palmarini, Kevan M. Shokat, Adolfo García-Sastre, Jeremy A. Rassen, Robert Grosse, Oren S. Rosenberg, Kliment A. Verba, Christopher F. Basler, Marco Vignuzzi, Andrew A. Peden, Pedro Beltrao, Nevan J. Krogan

Materials/Methods, Supplementary Text, Tables, Figures, and/or References

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  • QCRG Structural Biology Consortium Author List
  • Zoonomia Consortium Author List
  • Figs. S1 to S25
  • Captions for Tables S1 to S15
  • Caption for Movie S1
  • References
Table S1
Protein sequence similarity. Protein sequence similarities for SARS-CoV-2:SARSCoV- 1, SARS-CoV-2:MERS, SARS-CoV-1:SARS-CoV-2 and MERS:SARS-CoV-2. Identities are only presented for genes with the same name in the compared virus pairs.
Table S2
Unthresholded and high-confidence virus-host protein interactions. Contains unthresholded (SARS-CoV-2_Unthresholded, SARS-CoV-1_Unthresholded, and MERSCoV_ Unthresholded tabs) as well as high-confidence (SARS-CoV-2_HighConfidence, SARSCoV- 1_HighConfidence, and MERS-CoV_HighConfidence tabs) virus-host protein interaction data from affinity purification-mass spectrometry (AP-MS) studies. Column descriptions are indicated in the final tab.
Table S3
Information on localization of viral proteins derived from immunolocalization experiments and predictions. The localization information for each of the viral proteins studied by immunostaining and sequence based predictions. It also includes information on use and validation of the anti-SARS-CoV-2 protein anti-sera.
Table S4
GO enrichment analysis results. Includes significantly enriched GO terms associated with each cluster and high-confidence interactors of each virus.
Table S5
Clustering and differential interaction scores. Contains virus-host interactions defined as high confidence for at least one virus. Only interactions involving viral bait proteins shared across all three viruses are considered. Differential interaction scores for all comparisons are included (SARS-CoV-1:MERS-CoV, SARS-CoV-2:MERS-CoV, SARS-CoV-2:SARS-CoV1, SARS-CoV-1-and-2:MERS-CoV). MiST scores, Saint scores (Saint score, BFDR, FoldChange), and average spectral counts for each interaction are also included.
Table S6
A549-ACE2 siRNA knockdown data. Includes averaged Z-scores, unaveraged Zscores, viabilities and knockdown efficiencies.
Table S7
Caco-2 CRISPR knockout data. Includes averaged Z-scores, unaveraged Z-scores and editing efficiencies.
Table S8
Statistics of the Orf9b-Tom70 cryoEM structure presented in this work.
Table S9
Statistics relating to genetic analysis of soluble IL17RA in COVID Host Genetics Initiative data.
Table S10
Sourcing of drugs for in vitro analysis with literature affinity values and measured SARS-CoV-2 IC50 values.
Table S11
Drug list, matching criteria, outcomes and comparative data for real-world comparison of host factor-targeting drugs.
Table S12
siRNA library sequences.
Table S13
siRNA library qPCR primers.
Table S14
sgRNA library sequences.
Table S15
Cas9 knockout amplicon PCR and sequencing primers.
MDAR Reproducibility Checklist

Images, Video, and Other Media

Movie S1
Conformational change between yeast Tom71 (without substrate) and Orf9bbound human Tom70 focusing on the core domain. Movie starts with just the core domain of yeast Tom71 substrate free structure (PDB:3FP3(96)) shown as white ribbon and then interpolates the core domain to our Orf9b-Tom70 structure (Tom70 in green, Orf9b in orange).