Proteomics of SARS-CoV-2 infected host cells reveals therapy targets
By D. Bojkova, Kevin Klann, B. Koch, M. Widera, David Krause, S. Ciesek, J. Cinatl, Christian Münch. Nature, 2020
900 citations recorded by the source corpus.
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. SARS-CoV-2 modulates central cellular pathways, such as translation, splicing, carbon metabolism, proteostasis and nucleic acid metabolism, in human cells; these pathways can be inhibited by small-molecule inhibitors to prevent viral replication in the cells.
Subfields: Infectious Diseases, Molecular Biology
View Paper: https://www.semanticscholar.org/paper/797d090ebfb244286bb65b2c42d37c9772c9ab89
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Citations in the corpus
- A SARS-CoV-2 Protein Interaction Map Reveals Targets for Drug-Repurposing (2020, positive): “We studied the interacting human proteins with regards to their biological functions, anatomical expression patterns, expression changes during SARS-CoV-2 infection 16 and in relation to other maps of host– pathogen interacting proteins 15,17 (Fig.”
- Papain-like protease regulates SARS-CoV-2 viral spread and innate immunity (2020, positive): “SARS-CoV-2 FFM1 stocks used in the experiments had undergone one passage on CaCo-2 cells, as described previously 25 .”
- SARS-CoV-2 binds platelet ACE2 to enhance thrombosis in COVID-19 (2020, result): “These levels were similar to the human colon cell line Caco-2 and the human lung cell line Calu-3, which are used as SARS-CoV-2-infected host cells [52, 53].”