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  1. Article ; Online: Characterization of Particle Size Distributions and Water-Soluble Ions in Particulate Matter Measured at a Broiler Farm

    Silva, Philip J. / Cress, Tanner / Drover, Ryan / Michael, Cara / Docekal, Gregory / Larkin, Pierce / Godoy, Antonio / Cavero, Devin A. / Sin, Crystal / Waites, Janise / Mahmood, Rezaul / Cohron, Martin / Purvis-Roberts, Kathleen L.

    Agriculture. 2023 June 22, v. 13, no. 7 p.1284-

    2023  

    Abstract: The chemical composition and size distribution of particulate matter produced at broiler poultry houses is not well understood, so this is a novel study to understand the particulate size distributions at a poultry house as well as the ionic composition ... ...

    Abstract The chemical composition and size distribution of particulate matter produced at broiler poultry houses is not well understood, so this is a novel study to understand the particulate size distributions at a poultry house as well as the ionic composition of the particulate matter using real-time methods. Two optical particle counters provided particle size distributions inside and outside the house. An ambient ion monitor and a particle-in-liquid sampler analyzed the ionic chemical composition of the particulate matter in the house while a scanning mobility particle sizer provided size information in the nanoparticle range. Ammonia concentrations in the house were measured using a chemical sensor. Ammonia concentrations in the house were consistently in the lower part of the per million range 2–20 ppm. The optical particle counter and ion chromatography measurements both showed a strong
    Keywords agriculture ; ammonia ; chemical composition ; diurnal variation ; farms ; ion exchange chromatography ; nanoparticles ; particle size ; particulates ; poultry ; poultry housing ; water solubility
    Language English
    Dates of publication 2023-0622
    Publishing place MDPI AG
    Document type Article ; Online
    Note Resource is Open Access
    ZDB-ID 2651678-0
    ISSN 2077-0472
    ISSN 2077-0472
    DOI 10.3390/agriculture13071284
    Database NAL-Catalogue (AGRICOLA)

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  2. Article ; Online: A functional map of HIV-host interactions in primary human T cells.

    Hiatt, Joseph / Hultquist, Judd F / McGregor, Michael J / Bouhaddou, Mehdi / Leenay, Ryan T / Simons, Lacy M / Young, Janet M / Haas, Paige / Roth, Theodore L / Tobin, Victoria / Wojcechowskyj, Jason A / Woo, Jonathan M / Rathore, Ujjwal / Cavero, Devin A / Shifrut, Eric / Nguyen, Thong T / Haas, Kelsey M / Malik, Harmit S / Doudna, Jennifer A /
    May, Andrew P / Marson, Alexander / Krogan, Nevan J

    Nature communications

    2022  Volume 13, Issue 1, Page(s) 1752

    Abstract: Human Immunodeficiency Virus (HIV) relies on host molecular machinery for replication. Systematic attempts to genetically or biochemically define these host factors have yielded hundreds of candidates, but few have been functionally validated in primary ... ...

    Abstract Human Immunodeficiency Virus (HIV) relies on host molecular machinery for replication. Systematic attempts to genetically or biochemically define these host factors have yielded hundreds of candidates, but few have been functionally validated in primary cells. Here, we target 426 genes previously implicated in the HIV lifecycle through protein interaction studies for CRISPR-Cas9-mediated knock-out in primary human CD4+ T cells in order to systematically assess their functional roles in HIV replication. We achieve efficient knockout (>50% of alleles) in 364 of the targeted genes and identify 86 candidate host factors that alter HIV infection. 47 of these factors validate by multiplex gene editing in independent donors, including 23 factors with restrictive activity. Both gene editing efficiencies and HIV-1 phenotypes are highly concordant among independent donors. Importantly, over half of these factors have not been previously described to play a functional role in HIV replication, providing numerous novel avenues for understanding HIV biology. These data further suggest that host-pathogen protein-protein interaction datasets offer an enriched source of candidates for functional host factor discovery and provide an improved understanding of the mechanics of HIV replication in primary T cells.
    MeSH term(s) CD4-Positive T-Lymphocytes/metabolism ; Gene Editing ; HIV Infections ; HIV-1/genetics ; Host Microbial Interactions/genetics ; Humans
    Language English
    Publishing date 2022-04-01
    Publishing country England
    Document type Journal Article ; Research Support, Non-U.S. Gov't ; Research Support, N.I.H., Extramural
    ZDB-ID 2553671-0
    ISSN 2041-1723 ; 2041-1723
    ISSN (online) 2041-1723
    ISSN 2041-1723
    DOI 10.1038/s41467-022-29346-w
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  3. Article ; Online: Efficient generation of isogenic primary human myeloid cells using CRISPR-Cas9 ribonucleoproteins.

    Hiatt, Joseph / Cavero, Devin A / McGregor, Michael J / Zheng, Weihao / Budzik, Jonathan M / Roth, Theodore L / Haas, Kelsey M / Wu, David / Rathore, Ujjwal / Meyer-Franke, Anke / Bouzidi, Mohamed S / Shifrut, Eric / Lee, Youjin / Kumar, Vigneshwari Easwar / Dang, Eric V / Gordon, David E / Wojcechowskyj, Jason A / Hultquist, Judd F / Fontaine, Krystal A /
    Pillai, Satish K / Cox, Jeffery S / Ernst, Joel D / Krogan, Nevan J / Marson, Alexander

    Cell reports

    2021  Volume 35, Issue 6, Page(s) 109105

    Abstract: Genome engineering of primary human cells with CRISPR-Cas9 has revolutionized experimental and therapeutic approaches to cell biology, but human myeloid-lineage cells have remained largely genetically intractable. We present a method for the delivery of ... ...

    Abstract Genome engineering of primary human cells with CRISPR-Cas9 has revolutionized experimental and therapeutic approaches to cell biology, but human myeloid-lineage cells have remained largely genetically intractable. We present a method for the delivery of CRISPR-Cas9 ribonucleoprotein (RNP) complexes by nucleofection directly into CD14
    MeSH term(s) Animals ; CRISPR-Cas Systems/genetics ; Genome/genetics ; Humans ; Mice ; Myeloid Cells/metabolism ; Ribonucleoproteins/metabolism
    Chemical Substances Ribonucleoproteins
    Language English
    Publishing date 2021-05-12
    Publishing country United States
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't
    ZDB-ID 2649101-1
    ISSN 2211-1247 ; 2211-1247
    ISSN (online) 2211-1247
    ISSN 2211-1247
    DOI 10.1016/j.celrep.2021.109105
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  4. Article ; Online: A SARS-CoV-2 protein interaction map reveals targets for drug repurposing.

    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

    Nature

    2020  Volume 583, Issue 7816, Page(s) 459–468

    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 ...

    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
    MeSH term(s) Animals ; Antiviral Agents/classification ; Antiviral Agents/pharmacology ; Betacoronavirus/drug effects ; Betacoronavirus/genetics ; Betacoronavirus/metabolism ; Betacoronavirus/pathogenicity ; COVID-19 ; Chlorocebus aethiops ; Cloning, Molecular ; Coronavirus Infections/drug therapy ; Coronavirus Infections/immunology ; Coronavirus Infections/metabolism ; Coronavirus Infections/virology ; 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 ; COVID-19 Drug Treatment
    Chemical Substances Antiviral Agents ; Receptors, sigma ; Viral Proteins ; SKP Cullin F-Box Protein Ligases (EC 2.3.2.27)
    Keywords covid19
    Language English
    Publishing date 2020-04-30
    Publishing country England
    Document type Journal Article ; Research Support, N.I.H., Extramural ; Research Support, Non-U.S. Gov't ; Research Support, U.S. Gov't, Non-P.H.S.
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/s41586-020-2286-9
    Database MEDical Literature Analysis and Retrieval System OnLINE

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  5. Article ; Online: A SARS-CoV-2-Human Protein-Protein Interaction Map Reveals Drug Targets and Potential Drug-Repurposing

    Gordon, David E. / Jang, Gwendolyn M. / Bouhaddou, Mehdi / Xu, Jiewei / Obernier, Kirsten / O'Meara, Matthew J / Guo, Jeffrey Z. / Swaney, Danielle L. / Tummino, Tia A. / Huttenhain, 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 / Naing, Zun Zar Chi / Zhou, Yuan / Peng, Shiming / Kirby, Ilsa T. / Melnyk, James E. / Chorba, John S / Lou, Kevin / Dai, Shizhong A. / Shen, Wenqi / Shi, Ying / Zhang, Ziyang / Barrio-Hernandez, Inigo / Memon, Danish / Hernandez-Armenta, Claudia / Mathy, Christopher J.P. / Perica, Tina / Pilla, Kala B. / Ganesan, Sai J. / Saltzberg, Daniel J. / Ramachandran, Rakesh / Liu, Xi / Rosenthal, Sara B. / Calviello, Lorenzo / Venkataramanan, Srivats / Liboy-Lugo, Jose / Lin, Yizhu / Wankowicz, Stephanie A. / Bohn, Markus / Sharp, Phillip P. / Trenker, Raphael / Young, Janet M. / Cavero, Devin A. / Hiatt, Joseph / Roth, Theo / Rathore, Ujjwal / Subramanian, Advait / Noack, Julia / Hubert, Mathieu / Roesch, Ferdinand / Vallet, Thomas / Meyer, Björn / White, Kris M. / Miorin, Lisa / Rosenberg, Oren S. / Verba, Kliment A. / Agard, David / Ott, Melanie / Emerman, Michael / Ruggero, Davide / Garcí-Sastre, Adolfo / Jura, Natalia / von Zastrow, Mark / Taunton, Jack / Ashworth, Alan / Schwartz, Olivier / Vignuzzi, Marco / d'Enfert, Christophe / Mukherjee, Shaeri / Jacobson, Matt / Malik, Harmit S. / Fujimori, Danica G / Ideker, Trey / Craik, Charles S / Floor, Stephen / Fraser, James S. / Gross, John / Sali, Andrej / Kortemme, Tanja / Beltrao, Pedro / Shokat, Kevan / Shoichet, Brian K. / Krogan, Nevan J.

    bioRxiv

    Abstract: 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. There are currently no ... ...

    Abstract 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. 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 expressed 26 of the 29 viral proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), which identified 332 high confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 67 druggable human proteins or host factors targeted by 69 existing FDA-approved drugs, drugs in clinical trials and/or preclinical compounds, 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 therapeutics against SARS-CoV-2 and other deadly coronavirus strains.
    Keywords covid19
    Language English
    Publishing date 2020-03-27
    Publisher Cold Spring Harbor Laboratory
    Document type Article ; Online
    DOI 10.1101/2020.03.22.002386
    Database COVID19

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  6. Article ; Online: A SARS-CoV-2 protein interaction map reveals targets for drug repurposing

    Gordon, David E. / Jang, Gwendolyn M. / Bouhaddou, Mehdi / Xu, Jiewei / Obernier, Kirsten / White, Kris M. / O'Meara, Matthew J. / Rezelj, Veronica V. / Gou, Jeffrey Z. / Swaney, Danielle L. / Tummino, Tia A. / Huttenhain, 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 / Naig, 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 / Barrio-Hernandez, Inigo / Memon, Danish / Hernandez-Armenta, Claudia / Lyu, Jiankun / Mathy, Christoper J.P. / Perica, Tina / Pilla, Kala B. / Ganesan, Sai J. / Salzberg, 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, Duygu / Wang, Hao-Yuan / Trenker, Raphael / Young, Janet M. / Cavero, Devin A. / Hiatt, Joseph / Roth, Theodore / Rathore, Ujjwal / Subramanian, Adavait / 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 / Jacobsen, 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 / Garcia-Sastre, Adolfo / Shokat, Kevan M. / Shoichet, Brian K. / Krogan, Nevan J.

    Nature

    2020  

    Abstract: The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 2.3 million people, killed over 160,000, and caused worldwide social and economic disruption1,2. There are currently no antiviral drugs with proven ... ...

    Abstract The novel coronavirus SARS-CoV-2, the causative agent of COVID-19 respiratory disease, has infected over 2.3 million people, killed over 160,000, and caused worldwide social and economic disruption1,2. There are currently no antiviral drugs with proven clinical efficacy, nor are there vaccines for its prevention, and these efforts are hampered by limited knowledge of the molecular details of SARS-CoV-2 infection. To address this, we cloned, tagged and expressed 26 of the 29 SARS-CoV-2 proteins in human cells and identified the human proteins physically associated with each using affinity-purification mass spectrometry (AP-MS), identifying 332 high-confidence SARS-CoV-2-human protein-protein interactions (PPIs). Among these, we identify 66 druggable human proteins or host factors targeted by 69 compounds (29 FDA-approved drugs, 12 drugs in clinical trials, and 28 preclinical compounds). Screening a subset of these in multiple viral assays identified two sets of pharmacological agents that displayed antiviral activity: inhibitors of mRNA translation and predicted regulators of the Sigma1 and Sigma2 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.
    Keywords covid19
    Subject code 572
    Language English
    Publishing country us
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  7. Article ; Online: A SARS-CoV-2 protein interaction map reveals targets for drug repurposing.

    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 JP / 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 CJ / 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

    Nature, vol 583, iss 7816

    2020  

    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 ...

    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 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.
    Keywords Vero Cells ; Animals ; Humans ; Pneumonia ; Viral ; Coronavirus Infections ; SKP Cullin F-Box Protein Ligases ; Receptors ; sigma ; Viral Proteins ; Antiviral Agents ; Drug Evaluation ; Preclinical ; Cloning ; Molecular ; Protein Interaction Mapping ; Protein Biosynthesis ; Protein Binding ; Mass Spectrometry ; Host-Pathogen Interactions ; Immunity ; Innate ; HEK293 Cells ; Drug Repositioning ; Pandemics ; Molecular Targeted Therapy ; Protein Interaction Maps ; Protein Domains ; Betacoronavirus ; Chlorocebus aethiops ; General Science & Technology ; covid19
    Subject code 572
    Publishing date 2020-07-01
    Publisher eScholarship, University of California
    Publishing country us
    Document type Article ; Online
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

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  8. Article ; Online: A SARS-CoV-2 protein interaction map reveals targets for drug repurposing

    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.

    Nature

    2020  Volume 583, Issue 7816, Page(s) 459–468

    Keywords Multidisciplinary ; covid19
    Language English
    Publisher Springer Science and Business Media LLC
    Publishing country us
    Document type Article ; Online
    ZDB-ID 120714-3
    ISSN 1476-4687 ; 0028-0836
    ISSN (online) 1476-4687
    ISSN 0028-0836
    DOI 10.1038/s41586-020-2286-9
    Database BASE - Bielefeld Academic Search Engine (life sciences selection)

    More links

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