Submitted by Avi Ma'ayan (Icahn School of Medicine at Mount Sinai, USA) on Jul 16 2020
Platform: ngs – Illumina NextSeq 500 (Homo sapiens)
Pubmed: None listed
Summary The pandemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has imposed a significant burden on the human population. To understand the virus and the disease it causes we sought to interfere with the transcriptional response of the infected host. Utilizing the expression pattern of SARS-CoV-2-infected cells, we identified a region in gene expression space that was unique to virus infection and inversely proportional to the transcriptional footprint of known compounds characterized in the Library of Integrated Network-based Cellular Signatures (LINCS). Here we demonstrate the successful identification of compounds that display efficacy in blocking SARS-CoV-2 replication based on their ability to counteract the virus-induced transcriptional landscape. These compounds were found to potently reduce viral load despite having no impact on viral entry or modulation of the host antiviral response in the absence of virus. RNA-Seq profiling implicated the induction of the cholesterol biosynthesis pathway as the underlying mechanism of inhibition and suggested that targeting this aspect of host biology may significantly reduce SARS-CoV-2 viral load.
ID | Title | Cell Type | Timepoint | Reported Virus | Virus Species | Exclusion Reason |
---|---|---|---|---|---|---|
GSM4675736 | Organoids_Amlodipine-1 | pancreatic cell line | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions Amlodopine treated |
|
GSM4675737 | Organoids_Amlodipine-2 | pancreatic cell line | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions Amlodopine treated |
|
GSM4675738 | Organoids_Amlodipine-3 | pancreatic cell line | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions Amlodopine treated |
|
GSM4675739 | Organoids_Berbamine-1 | pancreatic cell line | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions Berbamine treated |
|
GSM4675740 | Organoids_Berbamine-2 | pancreatic cell line | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions Berbamine treated |
|
GSM4675741 | Organoids_Berbamine-3 | pancreatic cell line | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions Berbamine treated |
|
GSM4675742 | Organoids_DMSO-1 | pancreatic cell line | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | ||
GSM4675743 | Organoids_DMSO-2 | pancreatic cell line | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | ||
GSM4675744 | Organoids_DMSO-3 | pancreatic cell line | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | ||
GSM4675745 | Organoids_Loperamide-1 | pancreatic cell line | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions Loperamide treated |
|
GSM4675746 | Organoids_Loperamide-2 | pancreatic cell line | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions Loperamide treated |
|
GSM4675747 | Organoids_Loperamide-3 | pancreatic cell line | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions Loperamide treated |
|
GSM4675748 | Organoids_MOCK-1 | pancreatic cell line | Mock | Uninfected | ||
GSM4675749 | Organoids_MOCK-2 | pancreatic cell line | Mock | Uninfected | ||
GSM4675750 | Organoids_MOCK-3 | pancreatic cell line | Mock | Uninfected | ||
GSM4675751 | Organoids_RS504393-1 | pancreatic cell line | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions RS504393 treated |
|
GSM4675752 | Organoids_RS504393-2 | pancreatic cell line | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions RS504393 treated |
|
GSM4675753 | Organoids_RS504393-3 | pancreatic cell line | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions RS504393 treated |
|
GSM4675754 | Organoids_Terfenadine-1 | pancreatic cell line | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions Terfenadine treated |
|
GSM4675755 | Organoids_Terfenadine-2 | pancreatic cell line | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions Terfenadine treated |
|
GSM4675756 | Organoids_Terfenadine-3 | pancreatic cell line | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions Terfenadine treated |
|
GSM4675757 | Organoids_Trifluoperazine-1 | pancreatic cell line | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions Trifluoperazine treated |
|
GSM4675758 | Organoids_Trifluoperazine-2 | pancreatic cell line | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions Trifluoperazine treated |
|
GSM4675759 | Organoids_Trifluoperazine-3 | pancreatic cell line | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions Trifluoperazine treated |
|
GSM4675760 | ACE2-A549-Amlodipine-COV2-1 | non-small cell lung adenocarcinoma cell line [A-549 ] | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions Amlodopine treated; ACE2 overexpressed |
|
GSM4675761 | ACE2-A549-Amlodipine-COV2-2 | non-small cell lung adenocarcinoma cell line [A-549 ] | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions Amlodopine treated; ACE2 overexpressed |
|
GSM4675762 | ACE2-A549-Amlodipine-COV2-3 | non-small cell lung adenocarcinoma cell line [A-549 ] | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions Amlodopine treated; ACE2 overexpressed |
|
GSM4675763 | ACE2-A549-Amoldipine-drugonly-1 | non-small cell lung adenocarcinoma cell line [A-549 ] | Mock | Uninfected | Extra interventions Amlodopine treated; ACE2 overexpressed |
|
GSM4675764 | ACE2-A549-Amoldipine-drugonly-2 | non-small cell lung adenocarcinoma cell line [A-549 ] | Mock | Uninfected | Extra interventions Amlodopine treated; ACE2 overexpressed |
|
GSM4675765 | ACE2-A549-Amoldipine-drugonly-3 | non-small cell lung adenocarcinoma cell line [A-549 ] | Mock | Uninfected | Extra interventions Amlodopine treated; ACE2 overexpressed |
|
GSM4675766 | ACE2-A549-Berbamine-COV2-1 | non-small cell lung adenocarcinoma cell line [A-549 ] | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions Berbamine treated; ACE2 overexpressed |
|
GSM4675767 | ACE2-A549-Berbamine-COV2-2 | non-small cell lung adenocarcinoma cell line [A-549 ] | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions Berbamine treated; ACE2 overexpressed |
|
GSM4675768 | ACE2-A549-Berbamine-COV2-3 | non-small cell lung adenocarcinoma cell line [A-549 ] | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions Berbamine treated; ACE2 overexpressed |
|
GSM4675769 | ACE2-A549-Berbamine-drugonly-1 | non-small cell lung adenocarcinoma cell line [A-549 ] | Mock | Uninfected | Extra interventions Berbamine treated; ACE2 overexpressed |
|
GSM4675770 | ACE2-A549-Berbamine-drugonly-2 | non-small cell lung adenocarcinoma cell line [A-549 ] | Mock | Uninfected | Extra interventions Berbamine treated; ACE2 overexpressed |
|
GSM4675771 | ACE2-A549-Berbamine-drugonly-3 | non-small cell lung adenocarcinoma cell line [A-549 ] | Mock | Uninfected | Extra interventions Berbamine treated; ACE2 overexpressed |
|
GSM4675772 | ACE2-A549-DMSO-COV2-1 | non-small cell lung adenocarcinoma cell line [A-549 ] | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions ACE2 overexpressed |
|
GSM4675773 | ACE2-A549-DMSO-COV2-2 | non-small cell lung adenocarcinoma cell line [A-549 ] | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions ACE2 overexpressed |
|
GSM4675774 | ACE2-A549-DMSO-COV2-3 | non-small cell lung adenocarcinoma cell line [A-549 ] | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions ACE2 overexpressed |
|
GSM4675775 | ACE2-A549-Loperamide-COV2-1 | non-small cell lung adenocarcinoma cell line [A-549 ] | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions Loperamide treated; ACE2 overexpressed |
|
GSM4675776 | ACE2-A549-Loperamide-COV2-2 | non-small cell lung adenocarcinoma cell line [A-549 ] | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions Loperamide treated; ACE2 overexpressed |
|
GSM4675777 | ACE2-A549-Loperamide-COV2-3 | non-small cell lung adenocarcinoma cell line [A-549 ] | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions Loperamide treated; ACE2 overexpressed |
|
GSM4675778 | ACE2-A549-Loperamide-drugonly-1 | non-small cell lung adenocarcinoma cell line [A-549 ] | Mock | Uninfected | Extra interventions Loperamide treated; ACE2 overexpressed |
|
GSM4675779 | ACE2-A549-Loperamide-drugonly-2 | non-small cell lung adenocarcinoma cell line [A-549 ] | Mock | Uninfected | Extra interventions Loperamide treated; ACE2 overexpressed |
|
GSM4675780 | ACE2-A549-Loperamide-drugonly-3 | non-small cell lung adenocarcinoma cell line [A-549 ] | Mock | Uninfected | Extra interventions Loperamide treated; ACE2 overexpressed |
|
GSM4675781 | ACE2-A549-Mock-1 | non-small cell lung adenocarcinoma cell line [A-549 ] | Mock | Uninfected | Extra interventions ACE2 overexpressed |
|
GSM4675782 | ACE2-A549-Mock-2 | non-small cell lung adenocarcinoma cell line [A-549 ] | Mock | Uninfected | Extra interventions ACE2 overexpressed |
|
GSM4675783 | ACE2-A549-Mock-3 | non-small cell lung adenocarcinoma cell line [A-549 ] | Mock | Uninfected | Extra interventions ACE2 overexpressed |
|
GSM4675784 | ACE2-A549-RS504393-COV2-1 | non-small cell lung adenocarcinoma cell line [A-549 ] | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions RS504393 treated; ACE2 overexpressed |
|
GSM4675785 | ACE2-A549-RS504393-COV2-2 | non-small cell lung adenocarcinoma cell line [A-549 ] | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions RS504393 treated; ACE2 overexpressed |
|
GSM4675786 | ACE2-A549-RS504393-COV2-3 | non-small cell lung adenocarcinoma cell line [A-549 ] | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions RS504393 treated; ACE2 overexpressed |
|
GSM4675787 | ACE2-A549-RS504393-drugonly-1 | non-small cell lung adenocarcinoma cell line [A-549 ] | Mock | Uninfected | Extra interventions RS504393 treated; ACE2 overexpressed |
|
GSM4675788 | ACE2-A549-RS504393-drugonly-2 | non-small cell lung adenocarcinoma cell line [A-549 ] | Mock | Uninfected | Extra interventions RS504393 treated; ACE2 overexpressed |
|
GSM4675789 | ACE2-A549-RS504393-drugonly-3 | non-small cell lung adenocarcinoma cell line [A-549 ] | Mock | Uninfected | Extra interventions RS504393 treated; ACE2 overexpressed |
|
GSM4675790 | ACE2-A549-Terfenadine-COV2-1 | non-small cell lung adenocarcinoma cell line [A-549 ] | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions Terfenadine treated; ACE2 overexpressed |
|
GSM4675791 | ACE2-A549-Terfenadine-COV2-2 | non-small cell lung adenocarcinoma cell line [A-549 ] | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions Terfenadine treated; ACE2 overexpressed |
|
GSM4675792 | ACE2-A549-Terfenadine-COV2-3 | non-small cell lung adenocarcinoma cell line [A-549 ] | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions Terfenadine treated; ACE2 overexpressed |
|
GSM4675793 | ACE2-A549-Terfenadine-drugonly-1 | non-small cell lung adenocarcinoma cell line [A-549 ] | Mock | Uninfected | Extra interventions Terfenadine treated; ACE2 overexpressed |
|
GSM4675794 | ACE2-A549-Terfenadine-drugonly-2 | non-small cell lung adenocarcinoma cell line [A-549 ] | Mock | Uninfected | Extra interventions Terfenadine treated; ACE2 overexpressed |
|
GSM4675795 | ACE2-A549-Terfenadine-drugonly-3 | non-small cell lung adenocarcinoma cell line [A-549 ] | Mock | Uninfected | Extra interventions Terfenadine treated; ACE2 overexpressed |
|
GSM4675796 | ACE2-A549-Trifluoperazine-COV2-1 | non-small cell lung adenocarcinoma cell line [A-549 ] | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions Trifluoperazone treated; ACE2 overexpressed |
|
GSM4675797 | ACE2-A549-Trifluoperazine-COV2-2 | non-small cell lung adenocarcinoma cell line [A-549 ] | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions Trifluoperazone treated; ACE2 overexpressed |
|
GSM4675798 | ACE2-A549-Trifluoperazine-COV2-3 | non-small cell lung adenocarcinoma cell line [A-549 ] | SARS-CoV-2 | Severe acute respiratory syndrome-related coronavirus | Extra interventions Trifluoperazone treated; ACE2 overexpressed |
|
GSM4675799 | ACE2-A549-Trifluoperazone-drugonly-1 | non-small cell lung adenocarcinoma cell line [A-549 ] | Mock | Uninfected | Extra interventions Trifluoperazone treated; ACE2 overexpressed |
|
GSM4675800 | ACE2-A549-Trifluoperazone-drugonly-2 | non-small cell lung adenocarcinoma cell line [A-549 ] | Mock | Uninfected | Extra interventions Trifluoperazone treated; ACE2 overexpressed |
|
GSM4675801 | ACE2-A549-Trifluoperazone-drugonly-3 | non-small cell lung adenocarcinoma cell line [A-549 ] | Mock | Uninfected | Extra interventions Trifluoperazone treated; ACE2 overexpressed |