A SARS-CoV-2 protein interaction map reveals targets for drug repurposing
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 disr...
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| Veröffentlicht in: | Nature (London) 2020-07, Vol.583 (7816), p.459-468 |
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| creator | Gordon, David E Jang, Gwendolyn M Bouhaddou, Mehdi Xu, Jiewei Obernier, Kirsten White, Kris M O'Meara, Matthew J Rezelj, Veronica V Guo, Jeffrey Z Swaney, Danielle L Tummino, Tia A Hüttenhain, Ruth Kaake, Robyn M Richards, Alicia L Tutuncuoglu, Beril Foussard, Helene Batra, Jyoti Haas, Kelsey Modak, Maya Kim, Minkyu Haas, Paige Polacco, Benjamin J Braberg, Hannes Fabius, Jacqueline M Eckhardt, Manon Soucheray, Margaret Bennett, Melanie J Cakir, Merve McGregor, Michael J Li, Qiongyu Meyer, Bjoern Roesch, Ferdinand Vallet, Thomas Mac Kain, Alice Miorin, Lisa Moreno, Elena Naing, Zun Zar Chi Zhou, Yuan Peng, Shiming Shi, Ying Zhang, Ziyang Shen, Wenqi Kirby, Ilsa T Melnyk, James E Chorba, John S Lou, Kevin Dai, Shizhong A Barrio-Hernandez, Inigo Memon, Danish Hernandez-Armenta, Claudia Lyu, Jiankun Mathy, Christopher J P Perica, Tina Pilla, Kala Bharath Ganesan, Sai J Saltzberg, Daniel J Rakesh, Ramachandran Liu, Xi Rosenthal, Sara B Calviello, Lorenzo Venkataramanan, Srivats Liboy-Lugo, Jose Lin, Yizhu Huang, Xi-Ping Liu, YongFeng Wankowicz, Stephanie A Bohn, Markus Safari, Maliheh Ugur, Fatima S Koh, Cassandra Savar, Nastaran Sadat Tran, Quang Dinh Shengjuler, Djoshkun Fletcher, Sabrina J O'Neal, Michael C Cai, Yiming Chang, Jason C J Broadhurst, David J Klippsten, Saker Sharp, Phillip P Wenzell, Nicole A Kuzuoglu-Ozturk, Duygu Wang, Hao-Yuan Trenker, Raphael Young, Janet M Cavero, Devin A Hiatt, Joseph Roth, Theodore L Rathore, Ujjwal Subramanian, Advait Noack, Julia Hubert, Mathieu Stroud, Robert M Frankel, Alan D Rosenberg, Oren S Verba, Kliment A Agard, David A Ott, Melanie Emerman, Michael Jura, Natalia |
| description | 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
. 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. |
| doi_str_mv | 10.1038/s41586-020-2286-9 |
| format | Article |
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Jang, Gwendolyn M ; Bouhaddou, Mehdi ; Xu, Jiewei ; Obernier, Kirsten ; White, Kris M ; O'Meara, Matthew J ; Rezelj, Veronica V ; Guo, Jeffrey Z ; Swaney, Danielle L ; Tummino, Tia A ; Hüttenhain, Ruth ; Kaake, Robyn M ; Richards, Alicia L ; Tutuncuoglu, Beril ; Foussard, Helene ; Batra, Jyoti ; Haas, Kelsey ; Modak, Maya ; Kim, Minkyu ; Haas, Paige ; Polacco, Benjamin J ; Braberg, Hannes ; Fabius, Jacqueline M ; Eckhardt, Manon ; Soucheray, Margaret ; Bennett, Melanie J ; Cakir, Merve ; McGregor, Michael J ; Li, Qiongyu ; Meyer, Bjoern ; Roesch, Ferdinand ; Vallet, Thomas ; Mac Kain, Alice ; Miorin, Lisa ; Moreno, Elena ; Naing, Zun Zar Chi ; Zhou, Yuan ; Peng, Shiming ; Shi, Ying ; Zhang, Ziyang ; Shen, Wenqi ; Kirby, Ilsa T ; Melnyk, James E ; Chorba, John S ; Lou, Kevin ; Dai, Shizhong A ; Barrio-Hernandez, Inigo ; Memon, Danish ; Hernandez-Armenta, Claudia ; Lyu, Jiankun ; Mathy, Christopher J P ; Perica, Tina ; Pilla, Kala Bharath ; Ganesan, Sai J ; Saltzberg, Daniel J ; Rakesh, Ramachandran ; Liu, Xi ; Rosenthal, Sara B ; Calviello, Lorenzo ; Venkataramanan, Srivats ; Liboy-Lugo, Jose ; Lin, Yizhu ; Huang, Xi-Ping ; Liu, YongFeng ; Wankowicz, Stephanie A ; Bohn, Markus ; Safari, Maliheh ; Ugur, Fatima S ; Koh, Cassandra ; Savar, Nastaran Sadat ; Tran, Quang Dinh ; Shengjuler, Djoshkun ; Fletcher, Sabrina J ; O'Neal, Michael C ; Cai, Yiming ; Chang, Jason C J ; Broadhurst, David J ; Klippsten, Saker ; Sharp, Phillip P ; Wenzell, Nicole A ; Kuzuoglu-Ozturk, Duygu ; Wang, Hao-Yuan ; Trenker, Raphael ; Young, Janet M ; Cavero, Devin A ; Hiatt, Joseph ; Roth, Theodore L ; Rathore, Ujjwal ; Subramanian, Advait ; Noack, Julia ; Hubert, Mathieu ; Stroud, Robert M ; Frankel, Alan D ; Rosenberg, Oren S ; Verba, Kliment A ; Agard, David A ; Ott, Melanie ; Emerman, Michael ; Jura, Natalia</creator><creatorcontrib>Gordon, David E ; Jang, Gwendolyn M ; Bouhaddou, Mehdi ; Xu, Jiewei ; Obernier, Kirsten ; White, Kris M ; O'Meara, Matthew J ; Rezelj, Veronica V ; Guo, Jeffrey Z ; Swaney, Danielle L ; Tummino, Tia A ; Hüttenhain, Ruth ; Kaake, Robyn M ; Richards, Alicia L ; Tutuncuoglu, Beril ; Foussard, Helene ; Batra, Jyoti ; Haas, Kelsey ; Modak, Maya ; Kim, Minkyu ; Haas, Paige ; Polacco, Benjamin J ; Braberg, Hannes ; Fabius, Jacqueline M ; Eckhardt, Manon ; Soucheray, Margaret ; Bennett, Melanie J ; Cakir, Merve ; McGregor, Michael J ; Li, Qiongyu ; Meyer, Bjoern ; Roesch, Ferdinand ; Vallet, Thomas ; Mac Kain, Alice ; Miorin, Lisa ; Moreno, Elena ; Naing, Zun Zar Chi ; Zhou, Yuan ; Peng, Shiming ; Shi, Ying ; Zhang, Ziyang ; Shen, Wenqi ; Kirby, Ilsa T ; Melnyk, James E ; Chorba, John S ; Lou, Kevin ; Dai, Shizhong A ; Barrio-Hernandez, Inigo ; Memon, Danish ; Hernandez-Armenta, Claudia ; Lyu, Jiankun ; Mathy, Christopher J P ; Perica, Tina ; Pilla, Kala Bharath ; Ganesan, Sai J ; Saltzberg, Daniel J ; Rakesh, Ramachandran ; Liu, Xi ; Rosenthal, Sara B ; Calviello, Lorenzo ; Venkataramanan, Srivats ; Liboy-Lugo, Jose ; Lin, Yizhu ; Huang, Xi-Ping ; Liu, YongFeng ; Wankowicz, Stephanie A ; Bohn, Markus ; Safari, Maliheh ; Ugur, Fatima S ; Koh, Cassandra ; Savar, Nastaran Sadat ; Tran, Quang Dinh ; Shengjuler, Djoshkun ; Fletcher, Sabrina J ; O'Neal, Michael C ; Cai, Yiming ; Chang, Jason C J ; Broadhurst, David J ; Klippsten, Saker ; Sharp, Phillip P ; Wenzell, Nicole A ; Kuzuoglu-Ozturk, Duygu ; Wang, Hao-Yuan ; Trenker, Raphael ; Young, Janet M ; Cavero, Devin A ; Hiatt, Joseph ; Roth, Theodore L ; Rathore, Ujjwal ; Subramanian, Advait ; Noack, Julia ; Hubert, Mathieu ; Stroud, Robert M ; Frankel, Alan D ; Rosenberg, Oren S ; Verba, Kliment A ; Agard, David A ; Ott, Melanie ; Emerman, Michael ; Jura, Natalia</creatorcontrib><description>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
. 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.</description><identifier>ISSN: 0028-0836</identifier><identifier>EISSN: 1476-4687</identifier><identifier>DOI: 10.1038/s41586-020-2286-9</identifier><identifier>PMID: 32353859</identifier><language>eng</language><publisher>England</publisher><subject>Animals ; Antiviral Agents - classification ; Antiviral Agents - pharmacology ; Betacoronavirus - drug effects ; Betacoronavirus - genetics ; Betacoronavirus - metabolism ; Betacoronavirus - pathogenicity ; Chlorocebus aethiops ; Cloning, Molecular ; Coronavirus Infections - drug therapy ; Coronavirus Infections - immunology ; Coronavirus Infections - metabolism ; Coronavirus Infections - virology ; COVID-19 ; COVID-19 Drug Treatment ; Drug Evaluation, Preclinical ; Drug Repositioning ; HEK293 Cells ; Host-Pathogen Interactions - drug effects ; Humans ; Immunity, Innate ; Mass Spectrometry ; Molecular Targeted Therapy ; Pandemics ; Pneumonia, Viral - drug therapy ; Pneumonia, Viral - immunology ; Pneumonia, Viral - metabolism ; Pneumonia, Viral - virology ; Protein Binding ; Protein Biosynthesis - drug effects ; Protein Domains ; Protein Interaction Mapping ; Protein Interaction Maps ; Receptors, sigma - metabolism ; SARS-CoV-2 ; SKP Cullin F-Box Protein Ligases - metabolism ; Vero Cells ; Viral Proteins - genetics ; Viral Proteins - metabolism</subject><ispartof>Nature (London), 2020-07, Vol.583 (7816), p.459-468</ispartof><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><orcidid>0000-0002-5686-0451 ; 0000-0001-8303-457X ; 0000-0002-5218-6690 ; 0000-0003-3152-8425 ; 0000-0003-4416-2303 ; 0000-0002-3128-5331 ; 0000-0002-9113-8181 ; 0000-0001-6119-6084 ; 0000-0003-0702-7778 ; 0000-0003-2509-2127 ; 0000-0002-1393-5476 ; 0000-0001-7196-5078 ; 0000-0001-7954-0306 ; 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0000-0001-9816-115X ; 0000-0002-2301-4558 ; 0000-0002-3970-9573 ; 0000-0003-1748-0517</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><link.rule.ids>230,315,781,785,886,27926,27927</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/32353859$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Gordon, David E</creatorcontrib><creatorcontrib>Jang, Gwendolyn M</creatorcontrib><creatorcontrib>Bouhaddou, Mehdi</creatorcontrib><creatorcontrib>Xu, Jiewei</creatorcontrib><creatorcontrib>Obernier, Kirsten</creatorcontrib><creatorcontrib>White, Kris M</creatorcontrib><creatorcontrib>O'Meara, Matthew J</creatorcontrib><creatorcontrib>Rezelj, Veronica V</creatorcontrib><creatorcontrib>Guo, Jeffrey Z</creatorcontrib><creatorcontrib>Swaney, Danielle L</creatorcontrib><creatorcontrib>Tummino, Tia A</creatorcontrib><creatorcontrib>Hüttenhain, Ruth</creatorcontrib><creatorcontrib>Kaake, Robyn M</creatorcontrib><creatorcontrib>Richards, Alicia L</creatorcontrib><creatorcontrib>Tutuncuoglu, Beril</creatorcontrib><creatorcontrib>Foussard, Helene</creatorcontrib><creatorcontrib>Batra, Jyoti</creatorcontrib><creatorcontrib>Haas, Kelsey</creatorcontrib><creatorcontrib>Modak, Maya</creatorcontrib><creatorcontrib>Kim, Minkyu</creatorcontrib><creatorcontrib>Haas, Paige</creatorcontrib><creatorcontrib>Polacco, Benjamin J</creatorcontrib><creatorcontrib>Braberg, Hannes</creatorcontrib><creatorcontrib>Fabius, Jacqueline M</creatorcontrib><creatorcontrib>Eckhardt, Manon</creatorcontrib><creatorcontrib>Soucheray, Margaret</creatorcontrib><creatorcontrib>Bennett, Melanie J</creatorcontrib><creatorcontrib>Cakir, Merve</creatorcontrib><creatorcontrib>McGregor, Michael J</creatorcontrib><creatorcontrib>Li, Qiongyu</creatorcontrib><creatorcontrib>Meyer, Bjoern</creatorcontrib><creatorcontrib>Roesch, Ferdinand</creatorcontrib><creatorcontrib>Vallet, Thomas</creatorcontrib><creatorcontrib>Mac Kain, Alice</creatorcontrib><creatorcontrib>Miorin, Lisa</creatorcontrib><creatorcontrib>Moreno, Elena</creatorcontrib><creatorcontrib>Naing, Zun Zar Chi</creatorcontrib><creatorcontrib>Zhou, Yuan</creatorcontrib><creatorcontrib>Peng, Shiming</creatorcontrib><creatorcontrib>Shi, Ying</creatorcontrib><creatorcontrib>Zhang, Ziyang</creatorcontrib><creatorcontrib>Shen, Wenqi</creatorcontrib><creatorcontrib>Kirby, Ilsa T</creatorcontrib><creatorcontrib>Melnyk, James E</creatorcontrib><creatorcontrib>Chorba, John S</creatorcontrib><creatorcontrib>Lou, Kevin</creatorcontrib><creatorcontrib>Dai, Shizhong A</creatorcontrib><creatorcontrib>Barrio-Hernandez, Inigo</creatorcontrib><creatorcontrib>Memon, Danish</creatorcontrib><creatorcontrib>Hernandez-Armenta, Claudia</creatorcontrib><creatorcontrib>Lyu, Jiankun</creatorcontrib><creatorcontrib>Mathy, Christopher J P</creatorcontrib><creatorcontrib>Perica, Tina</creatorcontrib><creatorcontrib>Pilla, Kala Bharath</creatorcontrib><creatorcontrib>Ganesan, Sai J</creatorcontrib><creatorcontrib>Saltzberg, Daniel J</creatorcontrib><creatorcontrib>Rakesh, Ramachandran</creatorcontrib><creatorcontrib>Liu, Xi</creatorcontrib><creatorcontrib>Rosenthal, Sara B</creatorcontrib><creatorcontrib>Calviello, Lorenzo</creatorcontrib><creatorcontrib>Venkataramanan, Srivats</creatorcontrib><creatorcontrib>Liboy-Lugo, Jose</creatorcontrib><creatorcontrib>Lin, Yizhu</creatorcontrib><creatorcontrib>Huang, Xi-Ping</creatorcontrib><creatorcontrib>Liu, YongFeng</creatorcontrib><creatorcontrib>Wankowicz, Stephanie A</creatorcontrib><creatorcontrib>Bohn, Markus</creatorcontrib><creatorcontrib>Safari, Maliheh</creatorcontrib><creatorcontrib>Ugur, Fatima S</creatorcontrib><creatorcontrib>Koh, Cassandra</creatorcontrib><creatorcontrib>Savar, Nastaran Sadat</creatorcontrib><creatorcontrib>Tran, Quang Dinh</creatorcontrib><creatorcontrib>Shengjuler, Djoshkun</creatorcontrib><creatorcontrib>Fletcher, Sabrina J</creatorcontrib><creatorcontrib>O'Neal, Michael C</creatorcontrib><creatorcontrib>Cai, Yiming</creatorcontrib><creatorcontrib>Chang, Jason C J</creatorcontrib><creatorcontrib>Broadhurst, David J</creatorcontrib><creatorcontrib>Klippsten, Saker</creatorcontrib><creatorcontrib>Sharp, Phillip P</creatorcontrib><creatorcontrib>Wenzell, Nicole A</creatorcontrib><creatorcontrib>Kuzuoglu-Ozturk, Duygu</creatorcontrib><creatorcontrib>Wang, Hao-Yuan</creatorcontrib><creatorcontrib>Trenker, Raphael</creatorcontrib><creatorcontrib>Young, Janet M</creatorcontrib><creatorcontrib>Cavero, Devin A</creatorcontrib><creatorcontrib>Hiatt, Joseph</creatorcontrib><creatorcontrib>Roth, Theodore L</creatorcontrib><creatorcontrib>Rathore, Ujjwal</creatorcontrib><creatorcontrib>Subramanian, Advait</creatorcontrib><creatorcontrib>Noack, Julia</creatorcontrib><creatorcontrib>Hubert, Mathieu</creatorcontrib><creatorcontrib>Stroud, Robert M</creatorcontrib><creatorcontrib>Frankel, Alan D</creatorcontrib><creatorcontrib>Rosenberg, Oren S</creatorcontrib><creatorcontrib>Verba, Kliment A</creatorcontrib><creatorcontrib>Agard, David A</creatorcontrib><creatorcontrib>Ott, Melanie</creatorcontrib><creatorcontrib>Emerman, Michael</creatorcontrib><creatorcontrib>Jura, Natalia</creatorcontrib><title>A SARS-CoV-2 protein interaction map reveals targets for drug repurposing</title><title>Nature (London)</title><addtitle>Nature</addtitle><description>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
. 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.</description><subject>Animals</subject><subject>Antiviral Agents - classification</subject><subject>Antiviral Agents - pharmacology</subject><subject>Betacoronavirus - drug effects</subject><subject>Betacoronavirus - genetics</subject><subject>Betacoronavirus - metabolism</subject><subject>Betacoronavirus - pathogenicity</subject><subject>Chlorocebus aethiops</subject><subject>Cloning, Molecular</subject><subject>Coronavirus Infections - drug therapy</subject><subject>Coronavirus Infections - immunology</subject><subject>Coronavirus Infections - metabolism</subject><subject>Coronavirus Infections - virology</subject><subject>COVID-19</subject><subject>COVID-19 Drug Treatment</subject><subject>Drug Evaluation, Preclinical</subject><subject>Drug Repositioning</subject><subject>HEK293 Cells</subject><subject>Host-Pathogen Interactions - drug effects</subject><subject>Humans</subject><subject>Immunity, Innate</subject><subject>Mass Spectrometry</subject><subject>Molecular Targeted Therapy</subject><subject>Pandemics</subject><subject>Pneumonia, Viral - drug therapy</subject><subject>Pneumonia, Viral - immunology</subject><subject>Pneumonia, Viral - metabolism</subject><subject>Pneumonia, Viral - virology</subject><subject>Protein Binding</subject><subject>Protein Biosynthesis - drug effects</subject><subject>Protein Domains</subject><subject>Protein Interaction Mapping</subject><subject>Protein Interaction Maps</subject><subject>Receptors, sigma - metabolism</subject><subject>SARS-CoV-2</subject><subject>SKP Cullin F-Box Protein Ligases - metabolism</subject><subject>Vero Cells</subject><subject>Viral Proteins - genetics</subject><subject>Viral Proteins - 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SARS-CoV-2 protein interaction map reveals targets for drug repurposing</title><author>Gordon, David E ; Jang, Gwendolyn M ; Bouhaddou, Mehdi ; Xu, Jiewei ; Obernier, Kirsten ; White, Kris M ; O'Meara, Matthew J ; Rezelj, Veronica V ; Guo, Jeffrey Z ; Swaney, Danielle L ; Tummino, Tia A ; Hüttenhain, Ruth ; Kaake, Robyn M ; Richards, Alicia L ; Tutuncuoglu, Beril ; Foussard, Helene ; Batra, Jyoti ; Haas, Kelsey ; Modak, Maya ; Kim, Minkyu ; Haas, Paige ; Polacco, Benjamin J ; Braberg, Hannes ; Fabius, Jacqueline M ; Eckhardt, Manon ; Soucheray, Margaret ; Bennett, Melanie J ; Cakir, Merve ; McGregor, Michael J ; Li, Qiongyu ; Meyer, Bjoern ; Roesch, Ferdinand ; Vallet, Thomas ; Mac Kain, Alice ; Miorin, Lisa ; Moreno, Elena ; Naing, Zun Zar Chi ; Zhou, Yuan ; Peng, Shiming ; Shi, Ying ; Zhang, Ziyang ; Shen, Wenqi ; Kirby, Ilsa T ; Melnyk, James E ; Chorba, John S ; Lou, Kevin ; Dai, Shizhong A ; Barrio-Hernandez, Inigo ; Memon, Danish ; Hernandez-Armenta, Claudia ; Lyu, Jiankun ; Mathy, Christopher J P ; Perica, Tina ; Pilla, Kala Bharath ; Ganesan, Sai J ; Saltzberg, Daniel J ; Rakesh, Ramachandran ; Liu, Xi ; Rosenthal, Sara B ; Calviello, Lorenzo ; Venkataramanan, Srivats ; Liboy-Lugo, Jose ; Lin, Yizhu ; Huang, Xi-Ping ; Liu, YongFeng ; Wankowicz, Stephanie A ; Bohn, Markus ; Safari, Maliheh ; Ugur, Fatima S ; Koh, Cassandra ; Savar, Nastaran Sadat ; Tran, Quang Dinh ; Shengjuler, Djoshkun ; Fletcher, Sabrina J ; O'Neal, Michael C ; Cai, Yiming ; Chang, Jason C J ; Broadhurst, David J ; Klippsten, Saker ; Sharp, Phillip P ; Wenzell, Nicole A ; Kuzuoglu-Ozturk, Duygu ; Wang, Hao-Yuan ; Trenker, Raphael ; Young, Janet M ; Cavero, Devin A ; Hiatt, Joseph ; Roth, Theodore L ; Rathore, Ujjwal ; Subramanian, Advait ; Noack, Julia ; Hubert, Mathieu ; Stroud, Robert M ; Frankel, Alan D ; Rosenberg, Oren S ; Verba, Kliment A ; Agard, David A ; Ott, Melanie ; Emerman, Michael ; Jura, Natalia</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-p163t-826332f1d07f058f19a7fdf5e6d18516a6582b766007bb57de2e59494697abbf3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Antiviral Agents - classification</topic><topic>Antiviral Agents - pharmacology</topic><topic>Betacoronavirus - drug effects</topic><topic>Betacoronavirus - genetics</topic><topic>Betacoronavirus - metabolism</topic><topic>Betacoronavirus - pathogenicity</topic><topic>Chlorocebus aethiops</topic><topic>Cloning, Molecular</topic><topic>Coronavirus Infections - drug therapy</topic><topic>Coronavirus Infections - immunology</topic><topic>Coronavirus Infections - metabolism</topic><topic>Coronavirus Infections - virology</topic><topic>COVID-19</topic><topic>COVID-19 Drug Treatment</topic><topic>Drug Evaluation, Preclinical</topic><topic>Drug Repositioning</topic><topic>HEK293 Cells</topic><topic>Host-Pathogen Interactions - drug effects</topic><topic>Humans</topic><topic>Immunity, Innate</topic><topic>Mass Spectrometry</topic><topic>Molecular Targeted Therapy</topic><topic>Pandemics</topic><topic>Pneumonia, Viral - drug therapy</topic><topic>Pneumonia, Viral - immunology</topic><topic>Pneumonia, Viral - metabolism</topic><topic>Pneumonia, Viral - virology</topic><topic>Protein Binding</topic><topic>Protein Biosynthesis - drug effects</topic><topic>Protein Domains</topic><topic>Protein Interaction Mapping</topic><topic>Protein Interaction Maps</topic><topic>Receptors, sigma - metabolism</topic><topic>SARS-CoV-2</topic><topic>SKP Cullin F-Box Protein Ligases - metabolism</topic><topic>Vero Cells</topic><topic>Viral Proteins - genetics</topic><topic>Viral Proteins - metabolism</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Gordon, David E</creatorcontrib><creatorcontrib>Jang, Gwendolyn 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E</creatorcontrib><creatorcontrib>Chorba, John S</creatorcontrib><creatorcontrib>Lou, Kevin</creatorcontrib><creatorcontrib>Dai, Shizhong A</creatorcontrib><creatorcontrib>Barrio-Hernandez, Inigo</creatorcontrib><creatorcontrib>Memon, Danish</creatorcontrib><creatorcontrib>Hernandez-Armenta, Claudia</creatorcontrib><creatorcontrib>Lyu, Jiankun</creatorcontrib><creatorcontrib>Mathy, Christopher J P</creatorcontrib><creatorcontrib>Perica, Tina</creatorcontrib><creatorcontrib>Pilla, Kala Bharath</creatorcontrib><creatorcontrib>Ganesan, Sai J</creatorcontrib><creatorcontrib>Saltzberg, Daniel J</creatorcontrib><creatorcontrib>Rakesh, Ramachandran</creatorcontrib><creatorcontrib>Liu, Xi</creatorcontrib><creatorcontrib>Rosenthal, Sara B</creatorcontrib><creatorcontrib>Calviello, Lorenzo</creatorcontrib><creatorcontrib>Venkataramanan, Srivats</creatorcontrib><creatorcontrib>Liboy-Lugo, Jose</creatorcontrib><creatorcontrib>Lin, Yizhu</creatorcontrib><creatorcontrib>Huang, 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(Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Nature (London)</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Gordon, David E</au><au>Jang, Gwendolyn M</au><au>Bouhaddou, Mehdi</au><au>Xu, Jiewei</au><au>Obernier, Kirsten</au><au>White, Kris M</au><au>O'Meara, Matthew J</au><au>Rezelj, Veronica V</au><au>Guo, Jeffrey Z</au><au>Swaney, Danielle L</au><au>Tummino, Tia A</au><au>Hüttenhain, Ruth</au><au>Kaake, Robyn M</au><au>Richards, Alicia L</au><au>Tutuncuoglu, Beril</au><au>Foussard, Helene</au><au>Batra, Jyoti</au><au>Haas, Kelsey</au><au>Modak, Maya</au><au>Kim, Minkyu</au><au>Haas, Paige</au><au>Polacco, Benjamin J</au><au>Braberg, Hannes</au><au>Fabius, Jacqueline M</au><au>Eckhardt, Manon</au><au>Soucheray, Margaret</au><au>Bennett, Melanie J</au><au>Cakir, Merve</au><au>McGregor, Michael J</au><au>Li, Qiongyu</au><au>Meyer, Bjoern</au><au>Roesch, Ferdinand</au><au>Vallet, Thomas</au><au>Mac Kain, Alice</au><au>Miorin, Lisa</au><au>Moreno, Elena</au><au>Naing, Zun Zar Chi</au><au>Zhou, Yuan</au><au>Peng, Shiming</au><au>Shi, Ying</au><au>Zhang, Ziyang</au><au>Shen, Wenqi</au><au>Kirby, Ilsa T</au><au>Melnyk, James E</au><au>Chorba, John S</au><au>Lou, Kevin</au><au>Dai, Shizhong A</au><au>Barrio-Hernandez, Inigo</au><au>Memon, Danish</au><au>Hernandez-Armenta, Claudia</au><au>Lyu, Jiankun</au><au>Mathy, Christopher J P</au><au>Perica, Tina</au><au>Pilla, Kala Bharath</au><au>Ganesan, Sai J</au><au>Saltzberg, Daniel J</au><au>Rakesh, Ramachandran</au><au>Liu, Xi</au><au>Rosenthal, Sara B</au><au>Calviello, Lorenzo</au><au>Venkataramanan, Srivats</au><au>Liboy-Lugo, Jose</au><au>Lin, Yizhu</au><au>Huang, Xi-Ping</au><au>Liu, YongFeng</au><au>Wankowicz, Stephanie A</au><au>Bohn, Markus</au><au>Safari, Maliheh</au><au>Ugur, Fatima S</au><au>Koh, Cassandra</au><au>Savar, Nastaran Sadat</au><au>Tran, Quang Dinh</au><au>Shengjuler, Djoshkun</au><au>Fletcher, Sabrina J</au><au>O'Neal, Michael C</au><au>Cai, Yiming</au><au>Chang, Jason C J</au><au>Broadhurst, David J</au><au>Klippsten, Saker</au><au>Sharp, Phillip P</au><au>Wenzell, Nicole A</au><au>Kuzuoglu-Ozturk, Duygu</au><au>Wang, Hao-Yuan</au><au>Trenker, Raphael</au><au>Young, Janet M</au><au>Cavero, Devin A</au><au>Hiatt, Joseph</au><au>Roth, Theodore L</au><au>Rathore, Ujjwal</au><au>Subramanian, Advait</au><au>Noack, Julia</au><au>Hubert, Mathieu</au><au>Stroud, Robert M</au><au>Frankel, Alan D</au><au>Rosenberg, Oren S</au><au>Verba, Kliment A</au><au>Agard, David A</au><au>Ott, Melanie</au><au>Emerman, Michael</au><au>Jura, Natalia</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>A SARS-CoV-2 protein interaction map reveals targets for drug repurposing</atitle><jtitle>Nature (London)</jtitle><addtitle>Nature</addtitle><date>2020-07-16</date><risdate>2020</risdate><volume>583</volume><issue>7816</issue><spage>459</spage><epage>468</epage><pages>459-468</pages><issn>0028-0836</issn><eissn>1476-4687</eissn><abstract>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
. 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.</abstract><cop>England</cop><pmid>32353859</pmid><doi>10.1038/s41586-020-2286-9</doi><tpages>10</tpages><orcidid>https://orcid.org/0000-0002-5686-0451</orcidid><orcidid>https://orcid.org/0000-0001-8303-457X</orcidid><orcidid>https://orcid.org/0000-0002-5218-6690</orcidid><orcidid>https://orcid.org/0000-0003-3152-8425</orcidid><orcidid>https://orcid.org/0000-0003-4416-2303</orcidid><orcidid>https://orcid.org/0000-0002-3128-5331</orcidid><orcidid>https://orcid.org/0000-0002-9113-8181</orcidid><orcidid>https://orcid.org/0000-0001-6119-6084</orcidid><orcidid>https://orcid.org/0000-0003-0702-7778</orcidid><orcidid>https://orcid.org/0000-0003-2509-2127</orcidid><orcidid>https://orcid.org/0000-0002-1393-5476</orcidid><orcidid>https://orcid.org/0000-0001-7196-5078</orcidid><orcidid>https://orcid.org/0000-0001-7954-0306</orcidid><orcidid>https://orcid.org/0000-0002-6320-5084</orcidid><orcidid>https://orcid.org/0000-0003-2466-6731</orcidid><orcidid>https://orcid.org/0000-0002-6293-8008</orcidid><orcidid>https://orcid.org/0000-0001-9317-1658</orcidid><orcidid>https://orcid.org/0000-0002-8327-1687</orcidid><orcidid>https://orcid.org/0000-0002-9749-6756</orcidid><orcidid>https://orcid.org/0000-0002-8657-4931</orcidid><orcidid>https://orcid.org/0000-0001-5129-641X</orcidid><orcidid>https://orcid.org/0000-0003-1570-9234</orcidid><orcidid>https://orcid.org/0000-0002-7070-2257</orcidid><orcidid>https://orcid.org/0000-0003-4939-4381</orcidid><orcidid>https://orcid.org/0000-0002-3905-2671</orcidid><orcidid>https://orcid.org/0000-0001-9155-820X</orcidid><orcidid>https://orcid.org/0000-0002-6548-9658</orcidid><orcidid>https://orcid.org/0000-0002-9263-0733</orcidid><orcidid>https://orcid.org/0000-0002-5600-0988</orcidid><orcidid>https://orcid.org/0000-0002-4225-7459</orcidid><orcidid>https://orcid.org/0000-0003-0541-7211</orcidid><orcidid>https://orcid.org/0000-0002-0896-5910</orcidid><orcidid>https://orcid.org/0000-0002-9263-4320</orcidid><orcidid>https://orcid.org/0000-0002-5736-4388</orcidid><orcidid>https://orcid.org/0000-0002-4869-2945</orcidid><orcidid>https://orcid.org/0000-0002-2507-401X</orcidid><orcidid>https://orcid.org/0000-0003-0889-0506</orcidid><orcidid>https://orcid.org/0000-0002-6286-9727</orcidid><orcidid>https://orcid.org/0000-0003-1803-5693</orcidid><orcidid>https://orcid.org/0000-0001-7775-7448</orcidid><orcidid>https://orcid.org/0000-0002-4025-1299</orcidid><orcidid>https://orcid.org/0000-0002-0670-6683</orcidid><orcidid>https://orcid.org/0000-0002-5458-2988</orcidid><orcidid>https://orcid.org/0000-0002-5063-113X</orcidid><orcidid>https://orcid.org/0000-0003-3512-695X</orcidid><orcidid>https://orcid.org/0000-0002-4181-6335</orcidid><orcidid>https://orcid.org/0000-0002-6397-6348</orcidid><orcidid>https://orcid.org/0000-0001-8490-8793</orcidid><orcidid>https://orcid.org/0000-0003-1915-8089</orcidid><orcidid>https://orcid.org/0000-0002-5546-9733</orcidid><orcidid>https://orcid.org/0000-0002-8335-2866</orcidid><orcidid>https://orcid.org/0000-0001-5830-243X</orcidid><orcidid>https://orcid.org/0000-0002-9997-2285</orcidid><orcidid>https://orcid.org/0000-0001-9679-2353</orcidid><orcidid>https://orcid.org/0000-0001-8220-8427</orcidid><orcidid>https://orcid.org/0000-0002-8209-2249</orcidid><orcidid>https://orcid.org/0000-0002-2190-0177</orcidid><orcidid>https://orcid.org/0000-0002-1365-0710</orcidid><orcidid>https://orcid.org/0000-0001-9816-115X</orcidid><orcidid>https://orcid.org/0000-0002-2301-4558</orcidid><orcidid>https://orcid.org/0000-0002-3970-9573</orcidid><orcidid>https://orcid.org/0000-0003-1748-0517</orcidid><oa>free_for_read</oa></addata></record> |
| fulltext | fulltext |
| identifier | ISSN: 0028-0836 |
| ispartof | Nature (London), 2020-07, Vol.583 (7816), p.459-468 |
| issn | 0028-0836 1476-4687 |
| language | eng |
| recordid | cdi_pubmedcentral_primary_oai_pubmedcentral_nih_gov_7431030 |
| source | MEDLINE; Nature Journals Online; Alma/SFX Local Collection |
| subjects | Animals Antiviral Agents - classification Antiviral Agents - pharmacology Betacoronavirus - drug effects Betacoronavirus - genetics Betacoronavirus - metabolism Betacoronavirus - pathogenicity Chlorocebus aethiops Cloning, Molecular Coronavirus Infections - drug therapy Coronavirus Infections - immunology Coronavirus Infections - metabolism Coronavirus Infections - virology COVID-19 COVID-19 Drug Treatment Drug Evaluation, Preclinical Drug Repositioning HEK293 Cells Host-Pathogen Interactions - drug effects Humans Immunity, Innate Mass Spectrometry Molecular Targeted Therapy Pandemics Pneumonia, Viral - drug therapy Pneumonia, Viral - immunology Pneumonia, Viral - metabolism Pneumonia, Viral - virology Protein Binding Protein Biosynthesis - drug effects Protein Domains Protein Interaction Mapping Protein Interaction Maps Receptors, sigma - metabolism SARS-CoV-2 SKP Cullin F-Box Protein Ligases - metabolism Vero Cells Viral Proteins - genetics Viral Proteins - metabolism |
| title | A SARS-CoV-2 protein interaction map reveals targets for drug repurposing |
| url | https://sfx.bib-bvb.de/sfx_tum?ctx_ver=Z39.88-2004&ctx_enc=info:ofi/enc:UTF-8&ctx_tim=2024-12-18T06%3A46%3A07IST&url_ver=Z39.88-2004&url_ctx_fmt=infofi/fmt:kev:mtx:ctx&rfr_id=info:sid/primo.exlibrisgroup.com:primo3-Article-pubmed&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.genre=article&rft.atitle=A%20SARS-CoV-2%20protein%20interaction%20map%20reveals%20targets%20for%20drug%20repurposing&rft.jtitle=Nature%20(London)&rft.au=Gordon,%20David%20E&rft.date=2020-07-16&rft.volume=583&rft.issue=7816&rft.spage=459&rft.epage=468&rft.pages=459-468&rft.issn=0028-0836&rft.eissn=1476-4687&rft_id=info:doi/10.1038/s41586-020-2286-9&rft_dat=%3Cpubmed%3E32353859%3C/pubmed%3E%3Curl%3E%3C/url%3E&disable_directlink=true&sfx.directlink=off&sfx.report_link=0&rft_id=info:oai/&rft_id=info:pmid/32353859&rfr_iscdi=true |