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; 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; Phuong Nguyen; Joana Paulino; Komal Ishwar Pawar; Jessica K. Peters; Thomas H. Pospiech; 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; 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; 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

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 McGregor, Zeynep CakirGwendolyn 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, Phuong Nguyen, Joana Paulino, Komal Ishwar Pawar, Jessica K. Peters, Thomas H. Pospiech, 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, 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, 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^*

^*Corresponding author for this work

Pharmacology

Research output: Contribution to journal › Article › peer-review

489 Scopus citations

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 (US)
Article number	eabe9403
Journal	Science
Volume	370
Issue number	6521
DOIs	https://doi.org/10.1126/science.abe9403
State	Published - Dec 4 2020

ASJC Scopus subject areas

General

UN SDGs

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

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10.1126/science.abe9403

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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., McGregor, M., ... Krogan, N. J. (2020). Comparative host-coronavirus protein interaction networks reveal pan-viral disease mechanisms. Science, 370(6521), Article eabe9403. https://doi.org/10.1126/science.abe9403

@article{350f02cadd7648d1a89962aab1552497,

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 Naing, {Zun Zar Chi} and Pulido, {Ernst H.} and Ying Shi and Inigo Barrio-Hernandez and Danish Memon and Eirini Petsalaki and Alistair Dunham and Marrero, {Miguel Correa} and David Burke and Cassandra Koh and Thomas Vallet and Silvas, {Jesus A.} and Azumaya, {Caleigh M.} and Christian Billesb{\o}lle and Brilot, {Axel F.} and Campbell, {Melody G.} and Amy Diallo and Dickinson, {Miles Sasha} and Devan Diwanji and Nadia Herrera and Nick Hoppe and Kratochvil, {Huong T.} and Yanxin Liu and Merz, {Gregory E.} and Michelle Moritz and Nguyen, {Henry C.} and Carlos Nowotny and Cristina Puchades and Rizo, {Alexandrea N.} and Ursula Schulze-Gahmen and Smith, {Amber M.} and Ming Sun and Young, {Iris D.} and Jianhua Zhao and Daniel Asarnow and Justin Biel and Alisa Bowen and Braxton, {Julian R.} and Jen Chen and Chio, {Cynthia M.} and Chio, {Un Seng} and Ishan Deshpande and Loan Doan and Bryan Faust and Sebastian Flores and Mingliang Jin and Kate Kim and Lam, {Victor L.} and Fei Li and Junrui Li and Li, {Yen Li} and Yang Li and Xi Liu and Megan Lo and Lopez, {Kyle E.} and Melo, {Arthur A.} and Moss, {Frank R.} and Phuong Nguyen and Joana Paulino and Pawar, {Komal Ishwar} and Peters, {Jessica K.} and Pospiech, {Thomas H.} and Maliheh Safari and Smriti Sangwan and Kaitlin Schaefer and Thomas, {Paul V.} and Thwin, {Aye C.} and Raphael Trenker and Eric Tse and Tsui, {Tsz Kin Martin} and Feng Wang and Natalie Whitis and Zanlin Yu and Kaihua Zhang and Yang Zhang and Fengbo Zhou and Daniel Saltzberg and Hodder, {Anthony J.} and Shun-Shion, {Amber S.} and Williams, {Daniel M.} and White, {Kris M.} and Romel Rosales and Thomas Kehrer and Lisa Miorin and Elena Moreno and Patel, {Arvind H.} and Suzannah Rihn and Khalid, {Mir M.} and Albert Vallejo-Gracia and Parinaz Fozouni and Simoneau, {Camille R.} and Roth, {Theodore L.} and David Wu and Karim, {Mohd Anisul} and Maya Ghoussaini and Ian Dunham and Francesco Berardi and Sebastian Weigang and Maxime Chazal and Jisoo Park and James Logue and Marisa McGrath and Stuart Weston and Robert Haupt and Hastie, {C. James} and Matthew Elliott and Fiona Brown and Burness, {Kerry A.} and Elaine Reid and Mark Dorward and Clare Johnson and Wilkinson, {Stuart G.} and Anna Geyer and Giesel, {Daniel M.} and Carla Baillie and Samantha Raggett and Hannah Leech and Rachel Toth and Nicola Goodman and Keough, {Kathleen C.} and Lind, {Abigail L.} and Klesh, {Reyna J.} and Hemphill, {Kafi R.} and Jared Carlson-Stevermer and Jennifer Oki and Kevin Holden and Travis Maures and Pollard, {Katherine S.} and Andrej Sali and Agard, {David A.} and Yifan Cheng and Fraser, {James S.} and Adam Frost and Natalia Jura and Tanja Kortemme and Aashish Manglik and Southworth, {Daniel R.} and Stroud, {Robert M.} and Alessi, {Dario R.} and Paul Davies and Frieman, {Matthew B.} and Trey Ideker and Carmen Abate and Nolwenn Jouvenet and Georg Kochs and Brian Shoichet and Melanie Ott and Massimo Palmarini and Shokat, {Kevan M.} 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.}",

year = "2020",

month = dec,

day = "4",

doi = "10.1126/science.abe9403",

language = "English (US)",

volume = "370",

journal = "Science",

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, Naing, ZZC, Pulido, EH, Shi, Y, Barrio-Hernandez, I, Memon, D, Petsalaki, E, Dunham, A, Marrero, MC, Burke, D, Koh, C, Vallet, T, Silvas, JA, Azumaya, CM, Billesbølle, C, Brilot, AF, Campbell, MG, Diallo, A, Dickinson, MS, Diwanji, D, Herrera, N, Hoppe, N, Kratochvil, HT, Liu, Y, Merz, GE, Moritz, M, Nguyen, HC, Nowotny, C, Puchades, C, Rizo, AN, Schulze-Gahmen, U, Smith, AM, Sun, M, Young, ID, Zhao, J, Asarnow, D, Biel, J, Bowen, A, Braxton, JR, Chen, J, Chio, CM, Chio, US, Deshpande, I, Doan, L, Faust, B, Flores, S, Jin, M, Kim, K, Lam, VL, Li, F, Li, J, Li, YL, Li, Y, Liu, X, Lo, M, Lopez, KE, Melo, AA, Moss, FR, Nguyen, P, Paulino, J, Pawar, KI, Peters, JK, Pospiech, TH, Safari, M, Sangwan, S, Schaefer, K, Thomas, PV, Thwin, AC, Trenker, R, Tse, E, Tsui, TKM, Wang, F, Whitis, N, Yu, Z, Zhang, K, Zhang, Y, Zhou, F, Saltzberg, D, Hodder, AJ, Shun-Shion, AS, Williams, DM, White, KM, Rosales, R, Kehrer, T, Miorin, L, Moreno, E, Patel, AH, Rihn, S, Khalid, MM, Vallejo-Gracia, A, Fozouni, P, Simoneau, CR, Roth, TL, Wu, D, Karim, MA, Ghoussaini, M, Dunham, I, Berardi, F, Weigang, S, Chazal, M, Park, J, Logue, J, McGrath, M, Weston, S, Haupt, R, Hastie, CJ, Elliott, M, Brown, F, Burness, KA, Reid, E, Dorward, M, Johnson, C, Wilkinson, SG, Geyer, A, Giesel, DM, Baillie, C, Raggett, S, Leech, H, Toth, R, Goodman, N, Keough, KC, Lind, AL, Klesh, RJ, Hemphill, KR, Carlson-Stevermer, J, Oki, J, Holden, K, Maures, T, Pollard, KS, Sali, A, Agard, DA, Cheng, Y, Fraser, JS, Frost, A, Jura, N, Kortemme, T, Manglik, A, Southworth, DR, Stroud, RM, Alessi, DR, Davies, P, Frieman, MB, Ideker, T, Abate, C, Jouvenet, N, Kochs, G, Shoichet, B, Ott, M, Palmarini, M, Shokat, KM, 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, 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 - Naing, Zun Zar Chi

AU - Pulido, Ernst H.

AU - Shi, Ying

AU - Barrio-Hernandez, Inigo

AU - Memon, Danish

AU - Petsalaki, Eirini

AU - Dunham, Alistair

AU - Marrero, Miguel Correa

AU - Burke, David

AU - Koh, Cassandra

AU - Vallet, Thomas

AU - Silvas, Jesus A.

AU - Azumaya, Caleigh M.

AU - Billesbølle, Christian

AU - Brilot, Axel F.

AU - Campbell, Melody G.

AU - Diallo, Amy

AU - Dickinson, Miles Sasha

AU - Diwanji, Devan

AU - Herrera, Nadia

AU - Hoppe, Nick

AU - Kratochvil, Huong T.

AU - Liu, Yanxin

AU - Merz, Gregory E.

AU - Moritz, Michelle

AU - Nguyen, Henry C.

AU - Nowotny, Carlos

AU - Puchades, Cristina

AU - Rizo, Alexandrea N.

AU - Schulze-Gahmen, Ursula

AU - Smith, Amber M.

AU - Sun, Ming

AU - Young, Iris D.

AU - Zhao, Jianhua

AU - Asarnow, Daniel

AU - Biel, Justin

AU - Bowen, Alisa

AU - Braxton, Julian R.

AU - Chen, Jen

AU - Chio, Cynthia M.

AU - Chio, Un Seng

AU - Deshpande, Ishan

AU - Doan, Loan

AU - Faust, Bryan

AU - Flores, Sebastian

AU - Jin, Mingliang

AU - Kim, Kate

AU - Lam, Victor L.

AU - Li, Fei

AU - Li, Junrui

AU - Li, Yen Li

AU - Li, Yang

AU - Liu, Xi

AU - Lo, Megan

AU - Lopez, Kyle E.

AU - Melo, Arthur A.

AU - Moss, Frank R.

AU - Nguyen, Phuong

AU - Paulino, Joana

AU - Pawar, Komal Ishwar

AU - Peters, Jessica K.

AU - Pospiech, Thomas H.

AU - Safari, Maliheh

AU - Sangwan, Smriti

AU - Schaefer, Kaitlin

AU - Thomas, Paul V.

AU - Thwin, Aye C.

AU - Trenker, Raphael

AU - Tse, Eric

AU - Tsui, Tsz Kin Martin

AU - Wang, Feng

AU - Whitis, Natalie

AU - Yu, Zanlin

AU - Zhang, Kaihua

AU - Zhang, Yang

AU - Zhou, Fengbo

AU - Saltzberg, Daniel

AU - Hodder, Anthony J.

AU - Shun-Shion, Amber S.

AU - Williams, Daniel M.

AU - White, Kris M.

AU - Rosales, Romel

AU - Kehrer, Thomas

AU - Miorin, Lisa

AU - Moreno, Elena

AU - Patel, Arvind H.

AU - Rihn, Suzannah

AU - Khalid, Mir M.

AU - Vallejo-Gracia, Albert

AU - Fozouni, Parinaz

AU - Simoneau, Camille R.

AU - Roth, Theodore L.

AU - Wu, David

AU - Karim, Mohd Anisul

AU - Ghoussaini, Maya

AU - Dunham, Ian

AU - Berardi, Francesco

AU - Weigang, Sebastian

AU - Chazal, Maxime

AU - Park, Jisoo

AU - Logue, James

AU - McGrath, Marisa

AU - Weston, Stuart

AU - Haupt, Robert

AU - Hastie, C. James

AU - Elliott, Matthew

AU - Brown, Fiona

AU - Burness, Kerry A.

AU - Reid, Elaine

AU - Dorward, Mark

AU - Johnson, Clare

AU - Wilkinson, Stuart G.

AU - Geyer, Anna

AU - Giesel, Daniel M.

AU - Baillie, Carla

AU - Raggett, Samantha

AU - Leech, Hannah

AU - Toth, Rachel

AU - Goodman, Nicola

AU - Keough, Kathleen C.

AU - Lind, Abigail L.

AU - Klesh, Reyna J.

AU - Hemphill, Kafi R.

AU - Carlson-Stevermer, Jared

AU - Oki, Jennifer

AU - Holden, Kevin

AU - Maures, Travis

AU - Pollard, Katherine S.

AU - Sali, Andrej

AU - Agard, David A.

AU - Cheng, Yifan

AU - Fraser, James S.

AU - Frost, Adam

AU - Jura, Natalia

AU - Kortemme, Tanja

AU - Manglik, Aashish

AU - Southworth, Daniel R.

AU - Stroud, Robert M.

AU - Alessi, Dario R.

AU - Davies, Paul

AU - Frieman, Matthew B.

AU - Ideker, Trey

AU - Abate, Carmen

AU - Jouvenet, Nolwenn

AU - Kochs, Georg

AU - Shoichet, Brian

AU - Ott, Melanie

AU - Palmarini, Massimo

AU - Shokat, Kevan M.

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.

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.

UR - http://www.scopus.com/inward/record.url?scp=85097210203&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85097210203&partnerID=8YFLogxK

U2 - 10.1126/science.abe9403

DO - 10.1126/science.abe9403

M3 - Article

C2 - 33060197

AN - SCOPUS:85097210203

SN - 0036-8075

VL - 370

JO - Science

JF - Science

IS - 6521

M1 - eabe9403

ER -

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

Abstract

ASJC Scopus subject areas

UN SDGs

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