Comparative host-coronavirus protein interaction networks reveal pan-viral 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; Daniel M. Williams; C. James Hastie; Matthew Elliott; Fiona Brown; Kerry A. Burness; Elaine Reid; Carla Baillie; Samantha Raggett; Rachel Toth; Dario R. Alessi; Paul Davies; 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

doi:10.1126/science.abe9403

Comparative host-coronavirus protein interaction networks reveal pan-viral 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 McGregorZeynep 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, Daniel M. Williams, C. James Hastie, Matthew Elliott, Fiona Brown, Kerry A. Burness, Elaine Reid, Carla Baillie, Samantha Raggett, Rachel Toth, Dario R. Alessi, Paul Davies, Adolfo García-Sastre (Lead / Corresponding author), Jeremy A. Rassen (Lead / Corresponding author), Robert Grosse (Lead / Corresponding author), Oren S. Rosenberg (Lead / Corresponding author), Kliment A. Verba (Lead / Corresponding author), Christopher F. Basler (Lead / Corresponding author), Marco Vignuzzi (Lead / Corresponding author), Andrew A. Peden (Lead / Corresponding author), Pedro Beltrao (Lead / Corresponding author), Nevan J. Krogan (Lead / Corresponding author)

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Abstract

The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a grave threat to public health and the global economy. SARS-CoV-2 is closely related to the more lethal but less transmissible coronaviruses SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have carried out comparative viral-human proteinprotein interaction and viral protein localization analyses for all three viruses. Subsequent functional genetic screening identified host factors that functionally impinge on coronavirus proliferation, including Tom70, a mitochondrial chaperone protein that interacts with both SARS-CoV-1 and SARSCoV- 2 ORF9b, an interaction we structurally characterized using cryo-electron microscopy. Combining genetically validated host factors with both COVID-19 patient genetic data and medical billing records identified molecular mechanisms and potential drug treatments that merit further molecular and clinical study.

Original language	English
Article number	eabe9403
Number of pages	28
Journal	Science (New York, N.Y.)
Volume	370
Issue number	6521
Early online date	15 Oct 2020
DOIs	https://doi.org/10.1126/science.abe9403
Publication status	Published - 4 Dec 2020

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This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1126/science.abe9403Licence: CC BY

Final Published VersionFinal published version, 6.17 MBLicence: CC BY

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, Gordon, D. E., Hiatt, J., Bouhaddou, M., Rezelj, V. V., Ulferts, S., Braberg, H., Jureka, A. S., Obernier, K., Guo, J. Z., Batra, J., Kaake, R. M., Weckstein, A. R., Owens, T. W., Gupta, M., Pourmal, S., Titus, E. W., Cakir, M., Soucheray, M., ... Krogan, N. J. (2020). Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science (New York, N.Y.), 370(6521), Article eabe9403. https://doi.org/10.1126/science.abe9403

@article{42de7dd7b036469ab622b09d3c239ae7,

title = "Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms",

abstract = "The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a grave threat to public health and the global economy. SARS-CoV-2 is closely related to the more lethal but less transmissible coronaviruses SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have carried out comparative viral-human proteinprotein interaction and viral protein localization analyses for all three viruses. Subsequent functional genetic screening identified host factors that functionally impinge on coronavirus proliferation, including Tom70, a mitochondrial chaperone protein that interacts with both SARS-CoV-1 and SARSCoV- 2 ORF9b, an interaction we structurally characterized using cryo-electron microscopy. Combining genetically validated host factors with both COVID-19 patient genetic data and medical billing records identified molecular mechanisms and potential drug treatments that merit further molecular and clinical study.",

author = "Gordon, {David E.} and Joseph Hiatt and Mehdi Bouhaddou and Rezelj, {Veronica V.} and Svenja Ulferts and Hannes Braberg and Jureka, {Alexander S.} and Kirsten Obernier and Guo, {Jeffrey Z.} and Jyoti Batra and Kaake, {Robyn M.} and Weckstein, {Andrew R.} and Owens, {Tristan W.} and Meghna Gupta and Sergei Pourmal and Titus, {Erron W} and Merve Cakir and Margaret Soucheray and Michael McGregor and Zeynep Cakir and Gwendolyn Jang and O'Meara, {Matthew J.} and Tummino, {Tia A.} and Ziyang Zhang and Helene Foussard and Ajda Rojc and Yuan Zhou and Dmitry Kuchenov and Ruth H{\"u}ttenhain and Jiewei Xu and Manon Eckhardt and Swaney, {Danielle L.} and Fabius, {Jacqueline M.} and Manisha Ummadi and Beril Tutuncuoglu and Ujjwal Rathore and Maya Modak and Paige Haas and Haas, {Kelsey M.} and Williams, {Daniel M.} and Hastie, {C. James} and Matthew Elliott and Fiona Brown and Burness, {Kerry A.} and Elaine Reid and Carla Baillie and Samantha Raggett and Rachel Toth and Alessi, {Dario R.} and Paul Davies and Adolfo Garc{\'i}a-Sastre and Rassen, {Jeremy A.} and Robert Grosse and Rosenberg, {Oren S.} and Verba, {Kliment A.} and Basler, {Christopher F.} and Marco Vignuzzi and Peden, {Andrew A.} and Pedro Beltrao and Krogan, {Nevan J.}",

note = "Copyright {\textcopyright} 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).",

year = "2020",

month = dec,

day = "4",

doi = "10.1126/science.abe9403",

language = "English",

volume = "370",

journal = "Science (New York, N.Y.)",

issn = "0036-8075",

publisher = "American Association for the Advancement of Science",

number = "6521",

}

Gordon, DE, Hiatt, J, Bouhaddou, M, Rezelj, VV, Ulferts, S, Braberg, H, Jureka, AS, Obernier, K, Guo, JZ, Batra, J, Kaake, RM, Weckstein, AR, Owens, TW, Gupta, M, Pourmal, S, Titus, EW, Cakir, M, Soucheray, M, McGregor, M, Cakir, Z, Jang, G, O'Meara, MJ, Tummino, TA, Zhang, Z, Foussard, H, Rojc, A, Zhou, Y, Kuchenov, D, Hüttenhain, R, Xu, J, Eckhardt, M, Swaney, DL, Fabius, JM, Ummadi, M, Tutuncuoglu, B, Rathore, U, Modak, M, Haas, P, Haas, KM, Williams, DM, Hastie, CJ, Elliott, M, Brown, F, Burness, KA, Reid, E, Baillie, C, Raggett, S, Toth, R , Alessi, DR , Davies, P, García-Sastre, A, Rassen, JA, Grosse, R, Rosenberg, OS, Verba, KA, Basler, CF, Vignuzzi, M, Peden, AA & Beltrao, P & Krogan, NJ 2020, 'Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms', Science (New York, N.Y.), vol. 370, no. 6521, eabe9403. https://doi.org/10.1126/science.abe9403

TY - JOUR

T1 - Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms

AU - Gordon, David E.

AU - Hiatt, Joseph

AU - Bouhaddou, Mehdi

AU - Rezelj, Veronica V.

AU - Ulferts, Svenja

AU - Braberg, Hannes

AU - Jureka, Alexander S.

AU - Obernier, Kirsten

AU - Guo, Jeffrey Z.

AU - Batra, Jyoti

AU - Kaake, Robyn M.

AU - Weckstein, Andrew R.

AU - Owens, Tristan W.

AU - Gupta, Meghna

AU - Pourmal, Sergei

AU - Titus, Erron W

AU - Cakir, Merve

AU - Soucheray, Margaret

AU - McGregor, Michael

AU - Cakir, Zeynep

AU - Jang, Gwendolyn

AU - O'Meara, Matthew J.

AU - Tummino, Tia A.

AU - Zhang, Ziyang

AU - Foussard, Helene

AU - Rojc, Ajda

AU - Zhou, Yuan

AU - Kuchenov, Dmitry

AU - Hüttenhain, Ruth

AU - Xu, Jiewei

AU - Eckhardt, Manon

AU - Swaney, Danielle L.

AU - Fabius, Jacqueline M.

AU - Ummadi, Manisha

AU - Tutuncuoglu, Beril

AU - Rathore, Ujjwal

AU - Modak, Maya

AU - Haas, Paige

AU - Haas, Kelsey M.

AU - Williams, Daniel M.

AU - Hastie, C. James

AU - Elliott, Matthew

AU - Brown, Fiona

AU - Burness, Kerry A.

AU - Reid, Elaine

AU - Baillie, Carla

AU - Raggett, Samantha

AU - Toth, Rachel

AU - Alessi, Dario R.

AU - Davies, Paul

AU - García-Sastre, Adolfo

AU - Rassen, Jeremy A.

AU - Grosse, Robert

AU - Rosenberg, Oren S.

AU - Verba, Kliment A.

AU - Basler, Christopher F.

AU - Vignuzzi, Marco

AU - Peden, Andrew A.

AU - Beltrao, Pedro

AU - Krogan, Nevan J.

N1 - Copyright © 2020 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works. Distributed under a Creative Commons Attribution License 4.0 (CC BY).

PY - 2020/12/4

Y1 - 2020/12/4

N2 - The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a grave threat to public health and the global economy. SARS-CoV-2 is closely related to the more lethal but less transmissible coronaviruses SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have carried out comparative viral-human proteinprotein interaction and viral protein localization analyses for all three viruses. Subsequent functional genetic screening identified host factors that functionally impinge on coronavirus proliferation, including Tom70, a mitochondrial chaperone protein that interacts with both SARS-CoV-1 and SARSCoV- 2 ORF9b, an interaction we structurally characterized using cryo-electron microscopy. Combining genetically validated host factors with both COVID-19 patient genetic data and medical billing records identified molecular mechanisms and potential drug treatments that merit further molecular and clinical study.

AB - The COVID-19 pandemic, caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is a grave threat to public health and the global economy. SARS-CoV-2 is closely related to the more lethal but less transmissible coronaviruses SARS-CoV-1 and Middle East respiratory syndrome coronavirus (MERS-CoV). Here, we have carried out comparative viral-human proteinprotein interaction and viral protein localization analyses for all three viruses. Subsequent functional genetic screening identified host factors that functionally impinge on coronavirus proliferation, including Tom70, a mitochondrial chaperone protein that interacts with both SARS-CoV-1 and SARSCoV- 2 ORF9b, an interaction we structurally characterized using cryo-electron microscopy. Combining genetically validated host factors with both COVID-19 patient genetic data and medical billing records identified molecular mechanisms and potential drug treatments that merit further molecular and clinical study.

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U2 - 10.1126/science.abe9403

DO - 10.1126/science.abe9403

M3 - Article

C2 - 33060197

SN - 0036-8075

VL - 370

JO - Science (New York, N.Y.)

JF - Science (New York, N.Y.)

IS - 6521

M1 - eabe9403

ER -

Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms

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Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms

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ASJC Scopus subject areas

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