SARS-CoV-2 infected host cell proteomics reveal potential therapy targets

Abstract

Abstract A novel coronavirus was recently discovered and termed SARS-CoV-2. Human infection can cause coronavirus disease 2019 (COVID-19), for which, at this point, over 80,000 cases resulting in over 2,500 deaths have been reported in over 40 countries. 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-19 infection and reveal that drugs targeting 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 translatome 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 were tested in cellular infection assays and prevented viral replication. 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 develop therapy options for COVID-19.Authors Denisa Bojkova, Kevin Klann, and Benjamin Koch contributed equally to this workData associated with the preprint has been made available on the authors' website.