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Proteomics of SARS-CoV-2-infected host cells reveals therapy targets.
Nature. 2020 07; 583(7816):469-472.Nat

Abstract

A new coronavirus was recently discovered and named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Infection with SARS-CoV-2 in humans causes coronavirus disease 2019 (COVID-19) and has been rapidly spreading around the globe1,2. SARS-CoV-2 shows some similarities to other coronaviruses; however, treatment options and an understanding of how SARS-CoV-2 infects cells are lacking. Here we identify the host cell pathways that are modulated by SARS-CoV-2 and show that inhibition of these pathways prevents viral replication in human cells. We established a human cell-culture model for infection with a clinical isolate of SARS-CoV-2. Using this cell-culture system, we determined the infection profile of SARS-CoV-2 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, protein homeostasis (proteostasis) and nucleic acid metabolism. Small-molecule inhibitors that target these pathways prevented viral replication in cells. Our results reveal the cellular infection profile of SARS-CoV-2 and have enabled the identification of drugs that inhibit viral replication. We anticipate that our results will guide efforts to understand the molecular mechanisms that underlie the modulation of host cells after infection with SARS-CoV-2. Furthermore, our findings provide insights for the development of therapies for the treatment of 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
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

32408336

Citation

Bojkova, Denisa, et al. "Proteomics of SARS-CoV-2-infected Host Cells Reveals Therapy Targets." Nature, vol. 583, no. 7816, 2020, pp. 469-472.
Bojkova D, Klann K, Koch B, et al. Proteomics of SARS-CoV-2-infected host cells reveals therapy targets. Nature. 2020;583(7816):469-472.
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, 583(7816), 469-472. 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;583(7816):469-472. 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/pubmed PY - 2020/7/22/medline PY - 2020/5/15/entrez SP - 469 EP - 472 JF - Nature JO - Nature VL - 583 IS - 7816 N2 - A new coronavirus was recently discovered and named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Infection with SARS-CoV-2 in humans causes coronavirus disease 2019 (COVID-19) and has been rapidly spreading around the globe1,2. SARS-CoV-2 shows some similarities to other coronaviruses; however, treatment options and an understanding of how SARS-CoV-2 infects cells are lacking. Here we identify the host cell pathways that are modulated by SARS-CoV-2 and show that inhibition of these pathways prevents viral replication in human cells. We established a human cell-culture model for infection with a clinical isolate of SARS-CoV-2. Using this cell-culture system, we determined the infection profile of SARS-CoV-2 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, protein homeostasis (proteostasis) and nucleic acid metabolism. Small-molecule inhibitors that target these pathways prevented viral replication in cells. Our results reveal the cellular infection profile of SARS-CoV-2 and have enabled the identification of drugs that inhibit viral replication. We anticipate that our results will guide efforts to understand the molecular mechanisms that underlie the modulation of host cells after infection with SARS-CoV-2. Furthermore, our findings provide insights for the development of therapies for the treatment of 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 -