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Proteomics of SARS-CoV-2-infected host cells reveals therapy targets.
Nature. 2020 May 14 [Online ahead of print]Nat

Abstract

A novel coronavirus was recently discovered and termed SARS-CoV-2. Human infection can cause coronavirus disease 2019 (COVID-19), which has been rapidly spreading around the globe1,2. SARS-CoV-2 shows some similarities to other coronaviruses. However, treatment options and a cellular understanding of SARS-CoV-2 infection are lacking. Here we identify the host cell pathways modulated by SARS-CoV-2 infection and show that inhibition of these pathways prevent viral replication in human cells. We established a human cell culture model for infection with SARS-CoV-2 clinical isolate. Employing this system, we determined the SARS-CoV-2 infection profile by translatome3 and proteome proteomics at different times after infection. These analyses revealed that SARS-CoV-2 reshapes central cellular pathways, such as translation, splicing, carbon metabolism and nucleic acid metabolism. Small molecule inhibitors targeting these pathways prevented viral replication in cells. Our results reveal the cellular infection profile of SARS-CoV-2 and led to the identification of drugs inhibiting viral replication. We anticipate our results to guide efforts to understand the molecular mechanisms underlying host cell modulation upon SARS-CoV-2 infection. Furthermore, our findings provide insight for the development of therapy options for COVID-19.

Authors+Show Affiliations

Institute of Medical Virology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany.Institute of Biochemistry II, Faculty of Medicine, Goethe University, Frankfurt am Main, Germany.Medical Clinic III, Nephrology, University Hospital Frankfurt, Frankfurt am Main, Germany.Institute of Medical Virology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany.Institute of Biochemistry II, Faculty of Medicine, Goethe University, Frankfurt am Main, Germany.Institute of Medical Virology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany. German Centre for Infection Research (DZIF), External partner site Frankfurt, Frankfurt am Main, Germany.Institute of Medical Virology, University Hospital Frankfurt, Goethe University, Frankfurt am Main, Germany. cinatl@em.uni-frankfurt.de.Institute of Biochemistry II, Faculty of Medicine, Goethe University, Frankfurt am Main, Germany. ch.muench@em.uni-frankfurt.de. Frankfurt Cancer Institute, Frankfurt am Main, Germany. ch.muench@em.uni-frankfurt.de. Cardio-Pulmonary Institute, Frankfurt am Main, Germany. ch.muench@em.uni-frankfurt.de.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

32408336

Citation

Bojkova, Denisa, et al. "Proteomics of SARS-CoV-2-infected Host Cells Reveals Therapy Targets." Nature, 2020.
Bojkova D, Klann K, Koch B, et al. Proteomics of SARS-CoV-2-infected host cells reveals therapy targets. Nature. 2020.
Bojkova, D., Klann, K., Koch, B., Widera, M., Krause, D., Ciesek, S., Cinatl, J., & Münch, C. (2020). Proteomics of SARS-CoV-2-infected host cells reveals therapy targets. Nature. https://doi.org/10.1038/s41586-020-2332-7
Bojkova D, et al. Proteomics of SARS-CoV-2-infected Host Cells Reveals Therapy Targets. Nature. 2020 May 14; PubMed PMID: 32408336.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Proteomics of SARS-CoV-2-infected host cells reveals therapy targets. AU - Bojkova,Denisa, AU - Klann,Kevin, AU - Koch,Benjamin, AU - Widera,Marek, AU - Krause,David, AU - Ciesek,Sandra, AU - Cinatl,Jindrich, AU - Münch,Christian, Y1 - 2020/05/14/ PY - 2020/02/27/received PY - 2020/05/06/accepted PY - 2020/5/15/entrez PY - 2020/5/15/pubmed PY - 2020/5/15/medline JF - Nature JO - Nature N2 - A novel coronavirus was recently discovered and termed SARS-CoV-2. Human infection can cause coronavirus disease 2019 (COVID-19), which has been rapidly spreading around the globe1,2. SARS-CoV-2 shows some similarities to other coronaviruses. However, treatment options and a cellular understanding of SARS-CoV-2 infection are lacking. Here we identify the host cell pathways modulated by SARS-CoV-2 infection and show that inhibition of these pathways prevent viral replication in human cells. We established a human cell culture model for infection with SARS-CoV-2 clinical isolate. Employing this system, we determined the SARS-CoV-2 infection profile by translatome3 and proteome proteomics at different times after infection. These analyses revealed that SARS-CoV-2 reshapes central cellular pathways, such as translation, splicing, carbon metabolism and nucleic acid metabolism. Small molecule inhibitors targeting these pathways prevented viral replication in cells. Our results reveal the cellular infection profile of SARS-CoV-2 and led to the identification of drugs inhibiting viral replication. We anticipate our results to guide efforts to understand the molecular mechanisms underlying host cell modulation upon SARS-CoV-2 infection. Furthermore, our findings provide insight for the development of therapy options for COVID-19. SN - 1476-4687 UR - https://www.unboundmedicine.com/medline/citation/32408336/Proteomics_of_SARS-CoV-2-infected_host_cells_reveals_therapy_targets L2 - https://doi.org/10.1038/s41586-020-2332-7 DB - PRIME DP - Unbound Medicine ER -
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