Nature · 2020

A SARS-CoV-2 protein interaction map reveals targets for drug repurposing.

СтатьяПоддержка NIH: внешняя программаПоддержка исследования: вне правительства СШАПоддержка правительства СШАНазвание и аннотация: Перевод в очереди

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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, von Zastrow Mark, Verdin Eric, Ashworth Alan, Schwartz Olivier, d'Enfert Christophe, Mukherjee Shaeri, Jacobson Matt, Malik Harmit S, Fujimori Danica G, Ideker Trey, Craik Charles S, Floor Stephen N, Fraser James S, Gross John D, Sali Andrej, Roth Bryan L, Ruggero Davide, Taunton Jack, Kortemme Tanja, Beltrao Pedro, Vignuzzi Marco, García-Sastre Adolfo, Shokat Kevan M, Shoichet Brian K, Krogan Nevan J

Аннотация

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 disruption1,2. 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 SARS-CoV-2 protein interaction map reveals targets for drug repurposing.

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