Cited by 1,010SARS-CoV-2 and COVID-19 ResearchCOVID-19 Clinical Research StudiesAdvanced Proteomics Techniques and Applications

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Proteomics of SARS-CoV-2-infected host cells reveals therapy targets

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Bojkova, Denisa, Klann, Kevin, Koch, Benjamin, Widera, Marek, Krause, David, Ciesek, Sandra, Cinatl, Jindrich, Münch, Christian·2020·Nature

DOI 10.1038/s41586-020-2332-7PMC PMC7616921

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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 globe 1,2. 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 translatome 3 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.

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Authors: Bojkova, D., Klann, K., Koch, B., Widera, M., Krause, D., Ciesek, S., Cinatl, J., & Münch, C.
Affiliations: Goethe University Frankfurt (DE)
University Hospital Frankfurt (DE)
Corresponding author: Cinatl, Jindrich
Münch, Christian
ORCID: Klann, Kevin
Koch, Benjamin
Widera, Marek
Krause, David
Ciesek, Sandra
Cinatl, Jindrich
Münch, Christian
Venue: Nature
Publisher: Springer Science and Business Media LLC
Published: 2020-05-14
Volume: 583
Issue: 7816
Pages: 469-472
ISSN: 0028-0836 (ISSN-L)
1476-4687
DOI: 10.1038/s41586-020-2332-7
PMC: PMC7616921
OpenAlex: W3026002191
Cited by: 1,010
References: 53
Citations by year: 2026: 25 · 2025: 58 · 2024: 86 · 2023: 118 · 2022: 198 · 2021: 347 · 2020: 177
FWCI: 27.46
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.springer.com/tdm (tdm)
www.springer.com/tdm (vor)
Locations: Nature (publishedVersion)
Research Square (acceptedVersion, cc-by)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
RePEc: Research Papers in Economics (submittedVersion)
Publikationsdatenbank der Fraunhofer-Gesellschaft (Fraunhofer-Gesellschaft) (submittedVersion)
Fraunhofer-Publica (Fraunhofer-Gesellschaft) (submittedVersion)
Zenodo (CERN European Organization for Nuclear Research) (submittedVersion, cc-by)
Funders: Frankfurter Stiftung für krebskranke Kinder
Hilfe für krebskranke Kinder Frankfurt
European Commission
Deutsche Forschungsgemeinschaft (ERC StG 803565, MU 4216/1-1, CRC 1177)
Aventis Foundation
Topics: Health Sciences › Medicine › Infectious Diseases › SARS-CoV-2 and COVID-19 Research
Health Sciences › Medicine › Infectious Diseases › COVID-19 Clinical Research Studies
Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
Keywords: SARS-CoV-2, COVID-19 pandemic, viral replication, host-pathogen interaction, translation (biology), splicing, carbon metabolism, proteostasis, nucleic acid metabolism, small molecule inhibitors, antiviral drug targets, proteome, translatome
MeSH terms: Betacoronavirus, Proteostasis, COVID-19, SARS-CoV-2, COVID-19 Drug Treatment, Carbon, Drug Evaluation, Preclinical, Humans, Kinetics, Pneumonia, Viral, RNA Splicing, Time Factors, Protein Biosynthesis, Virus Replication, Coronavirus Infections, Caco-2 Cells, Proteome, Proteomics, Host-Pathogen Interactions, Pandemics, Molecular Targeted Therapy, In Vitro Techniques

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