Semantic Scholar Open Access 2020 3834 sitasi

A SARS-CoV-2 Protein Interaction Map Reveals Targets for Drug-Repurposing

D. Gordon Gwendolyn M. Jang Mehdi Bouhaddou Jiewei Xu K. Obernier +120 lainnya

Lihat Sumber DOI

Abstrak

A newly described coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), which is the causative agent of coronavirus disease 2019 (COVID-19), has infected over 2.3 million people, led to the death of more than 160,000 individuals and caused worldwide social and economic disruption 1 , 2 . There are no antiviral drugs with proven clinical efficacy for the treatment of COVID-19, nor are there any vaccines that prevent infection with SARS-CoV-2, and efforts to develop drugs and vaccines are hampered by the limited knowledge of the molecular details of how SARS-CoV-2 infects cells. Here we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins that physically associated with each of the SARS-CoV-2 proteins using affinity-purification mass spectrometry, identifying 332 high-confidence protein–protein interactions between SARS-CoV-2 and human proteins. Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (of which, 29 drugs are approved by the US Food and Drug Administration, 12 are in clinical trials and 28 are preclinical compounds). We screened a subset of these in multiple viral assays and found two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the sigma-1 and sigma-2 receptors. Further studies of these host-factor-targeting agents, including their combination with drugs that directly target viral enzymes, could lead to a therapeutic regimen to treat COVID-19. A human–SARS-CoV-2 protein interaction map highlights cellular processes that are hijacked by the virus and that can be targeted by existing drugs, including inhibitors of mRNA translation and predicted regulators of the sigma receptors.

Topik & Kata Kunci

Medicine

Penulis (125)

D. Gordon

Gwendolyn M. Jang

Mehdi Bouhaddou

Jiewei Xu

K. Obernier

K. White

Matthew J. O’Meara

V. Rezelj

Jeffrey Z. Guo

D. Swaney

Tia A. Tummino

Ruth Hüttenhain

Robyn M. Kaake

Alicia L. Richards

B. Tutuncuoglu

Helene Foussard

Jyoti Batra

Kelsey M. Haas

Mayank Modak

Minkyu Kim

Paige Haas

Benjamin J. Polacco

Hannes Braberg

Jacqueline M. Fabius

Manon Eckhardt

Margaret Soucheray

M. J. Bennett

Merve Cakir

Michael J. McGregor

Qiongyu Li

Bjoern Meyer

F. Roesch

T. Vallet

Alice Mac Kain

Lisa Miorin

Elena Moreno

Zun Zar Chi Naing

Yuan Zhou

S. Peng

Ying Shi

Ziyang Zhang

W. Shen

I. T. Kirby

James E. Melnyk

John S. Chorba

Kevin Lou

Shizhong A. Dai

Inigo Barrio‐Hernandez

Danish Memon

Claudia Hernandez-Armenta

Jiankun Lyu

Christopher J. P. Mathy

Tina Perica

K. B. Pilla

S. Ganesan

Daniel J. Saltzberg

R. Rakesh

Xi Liu

S. Rosenthal

Lorenzo Calviello

S. Venkataramanan

José M Liboy-Lugo

Yizhu Lin

Xi-Ping Huang

Yongfeng Liu

S. Wankowicz

M. Bohn

M. Safari

Fatima S. Ugur

Cassandra Koh

Nastaran Sadat Savar

Q. Tran

Djoshkun Shengjuler

S. Fletcher

M. C. O’Neal

Yiming Cai

Jason C. J. Chang

D. Broadhurst

Saker Klippsten

Phillip P. Sharp

Nicole A. Wenzell

Duygu Kuzuoglu-Ozturk

Hao-Yuan Wang

R. Trenker

Janet M. Young

D. A. Cavero

J. Hiatt

Theodore L. Roth

Ujjwal Rathore

Advait Subramanian

Julia Noack

Mathieu Hubert

R. Stroud

A. Frankel

O. Rosenberg

K. Verba

D. Agard

M. Ott

M. Emerman

N. Jura

M. von Zastrow

E. Verdin

A. Ashworth

O. Schwartz

C. d’Enfert

Shaeri Mukherjee

Matt Jacobson

Harmit S. Malik

D. Fujimori

T. Ideker

C. Craik

S. Floor

J. Fraser

J. Gross

A. Sali

B. Roth

D. Ruggero

J. Taunton

T. Kortemme

P. Beltrão

M. Vignuzzi

A. García‐Sastre

K. Shokat

B. Shoichet

N. Krogan

Format Sitasi

APA MLA BibTeX

Gordon, D., Jang, G.M., Bouhaddou, M., Xu, J., Obernier, K., White, K. et al. (2020). A SARS-CoV-2 Protein Interaction Map Reveals Targets for Drug-Repurposing. https://doi.org/10.1038/s41586-020-2286-9

@article{gordon2020, author = {D. Gordon and Gwendolyn M. Jang and Mehdi Bouhaddou and Jiewei Xu and K. Obernier and K. White and Matthew J. O’Meara and V. Rezelj and Jeffrey Z. Guo and D. Swaney and Tia A. Tummino and Ruth Hüttenhain and Robyn M. Kaake and Alicia L. Richards and B. Tutuncuoglu and Helene Foussard and Jyoti Batra and Kelsey M. Haas and Mayank Modak and Minkyu Kim and Paige Haas and Benjamin J. Polacco and Hannes Braberg and Jacqueline M. Fabius and Manon Eckhardt and Margaret Soucheray and M. J. Bennett and Merve Cakir and Michael J. McGregor and Qiongyu Li and Bjoern Meyer and F. Roesch and T. Vallet and Alice Mac Kain and Lisa Miorin and Elena Moreno and Zun Zar Chi Naing and Yuan Zhou and S. Peng and Ying Shi and Ziyang Zhang and W. Shen and I. T. Kirby and James E. Melnyk and John S. Chorba and Kevin Lou and Shizhong A. Dai and Inigo Barrio‐Hernandez and Danish Memon and Claudia Hernandez-Armenta and Jiankun Lyu and Christopher J. P. Mathy and Tina Perica and K. B. Pilla and S. Ganesan and Daniel J. Saltzberg and R. Rakesh and Xi Liu and S. Rosenthal and Lorenzo Calviello and S. Venkataramanan and José M Liboy-Lugo and Yizhu Lin and Xi-Ping Huang and Yongfeng Liu and S. Wankowicz and M. Bohn and M. Safari and Fatima S. Ugur and Cassandra Koh and Nastaran Sadat Savar and Q. Tran and Djoshkun Shengjuler and S. Fletcher and M. C. O’Neal and Yiming Cai and Jason C. J. Chang and D. Broadhurst and Saker Klippsten and Phillip P. Sharp and Nicole A. Wenzell and Duygu Kuzuoglu-Ozturk and Hao-Yuan Wang and R. Trenker and Janet M. Young and D. A. Cavero and J. Hiatt and Theodore L. Roth and Ujjwal Rathore and Advait Subramanian and Julia Noack and Mathieu Hubert and R. Stroud and A. Frankel and O. Rosenberg and K. Verba and D. Agard and M. Ott and M. Emerman and N. Jura and M. von Zastrow and E. Verdin and A. Ashworth and O. Schwartz and C. d’Enfert and Shaeri Mukherjee and Matt Jacobson and Harmit S. Malik and D. Fujimori and T. Ideker and C. Craik and S. Floor and J. Fraser and J. Gross and A. Sali and B. Roth and D. Ruggero and J. Taunton and T. Kortemme and P. Beltrão and M. Vignuzzi and A. García‐Sastre and K. Shokat and B. Shoichet and N. Krogan}, title = {A SARS-CoV-2 Protein Interaction Map Reveals Targets for Drug-Repurposing}, year = {2020}, journal = {Semantic Scholar}, doi = {10.1038/s41586-020-2286-9}, url = {https://www.semanticscholar.org/paper/bce3fd021c1d943708141caa37bfcf78fa157a38}, }

Akses Cepat

Lihat di Sumber doi.org/10.1038/s41586-020-2286-9

Informasi Jurnal

Tahun Terbit: 2020
Bahasa: en
Total Sitasi: 3834×
Sumber Database: Semantic Scholar
DOI: 10.1038/s41586-020-2286-9
Akses: Open Access ✓