Proteomics

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A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Purposing

ABSTRACT: An outbreak of the novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 170,000 people since the end of 2019, killed over 7,400, and caused worldwide social and economic disruption. SARS-CoV-2 infection has a mortality rate of 3.4% among confirmed cases, and there are currently no effective antiviral molecules or vaccines for its treatment or prevention. The search for effective antiviral treatments has recently highlighted host-directed strategies, however besides data describing viral interactions with cell surface receptors and activating proteases, the scientific community has little knowledge of the molecular details of SARS-CoV-2 infection. To shed light on the mechanisms used by SARS-CoV-2 to infect human cells, we have utilized affinity-purification mass spectrometry to globally profile physical host protein interactions for 26 viral proteins encoded in the SARS-CoV-2 genome, identifying 332 high confidence interactions. Among the human proteins, we identify many druggable human proteins targeted by existing FDA approved drugs that we are currently evaluating for efficacy in live SARS-CoV-2 infection assays. The identification of host-dependency factors mediating virus infection may provide key insights into effective molecular targets for developing broadly acting antiviral targets against SARS-CoV-2 and other deadly coronavirus strains.

INSTRUMENT(S): Exactive Plus

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Danielle Swaney  

LAB HEAD: Nevan Krogan

PROVIDER: PXD018117 | Pride | 2020-03-23

REPOSITORIES: Pride

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A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing.

Gordon David E DE   Jang Gwendolyn M GM   Bouhaddou Mehdi M   Xu Jiewei J   Obernier Kirsten K   O'Meara Matthew J MJ   Guo Jeffrey Z JZ   Swaney Danielle L DL   Tummino Tia A TA   Huettenhain Ruth R   Kaake Robyn M RM   Richards Alicia L AL   Tutuncuoglu Beril B   Foussard Helene H   Batra Jyoti J   Haas Kelsey K   Modak Maya M   Kim Minkyu M   Haas Paige P   Polacco Benjamin J BJ   Braberg Hannes H   Fabius Jacqueline M JM   Eckhardt Manon M   Soucheray Margaret M   Bennett Melanie J MJ   Cakir Merve M   McGregor Michael J MJ   Li Qiongyu Q   Naing Zun Zar Chi ZZC   Zhou Yuan Y   Peng Shiming S   Kirby Ilsa T IT   Melnyk James E JE   Chorba John S JS   Lou Kevin K   Dai Shizhong A SA   Shen Wenqi W   Shi Ying Y   Zhang Ziyang Z   Barrio-Hernandez Inigo I   Memon Danish D   Hernandez-Armenta Claudia C   Mathy Christopher J P CJP   Perica Tina T   Pilla Kala B KB   Ganesan Sai J SJ   Saltzberg Daniel J DJ   Ramachandran Rakesh R   Liu Xi X   Rosenthal Sara B SB   Calviello Lorenzo L   Venkataramanan Srivats S   Liboy-Lugo Jose J   Lin Yizhu Y   Wankowicz Stephanie A SA   Bohn Markus M   Sharp Phillip P PP   Trenker Raphael R   Young Janet M JM   Cavero Devin A DA   Hiatt Joseph J   Roth Theodore L TL   Rathore Ujjwal U   Subramanian Advait A   Noack Julia J   Hubert Mathieu M   Roesch Ferdinand F   Vallet Thomas T   Meyer Björn B   White Kris M KM   Miorin Lisa L   Rosenberg Oren S OS   Verba Kliment A KA   Agard David D   Ott Melanie M   Emerman Michael M   Ruggero Davide D   García-Sastre Adolfo A   Jura Natalia N   von Zastrow Mark M   Taunton Jack J   Taunton Jack J   Ashworth Alan A   Schwartz Olivier O   Vignuzzi Marco M   d'Enfert Christophe C   Mukherjee Shaeri S   Jacobson Matt M   Malik Harmit S HS   Fujimori Danica G DG   Ideker Trey T   Craik Charles S CS   Floor Stephen S   Fraser James S JS   Gross John J   Sali Andrej A   Kortemme Tanja T   Beltrao Pedro P   Shokat Kevan K   Shoichet Brian K BK   Krogan Nevan J NJ  

bioRxiv : the preprint server for biology 20200327

An outbreak of the novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 290,000 people since the end of 2019, killed over 12,000, and caused worldwide social and economic disruption<sup>1,2</sup>. There are currently no antiviral drugs with proven efficacy nor are there vaccines for its prevention. Unfortunately, the scientific community has little knowledge of the molecular details of SARS-CoV-2 infection. To illuminate this, we cloned, tagged and  ...[more]

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