Journal: Cell Reports

Article Title: Drug repurposing screens reveal cell-type-specific entry pathways and FDA-approved drugs active against SARS-Cov-2

doi: 10.1016/j.celrep.2021.108959

Figure Lengend Snippet: High-throughput screening in human Huh7.5 cells to identify antivirals against SARS-CoV-2 (A) Huh7.5 cells were infected with SARS-CoV-2 (MOI = 1) and 30 hpi processed for microscopy. (B) Dose-response analysis of Huh7.5 cells treated with hydroxychloroquine or remdesivir. Data represent the average of three independent experiments ± SD. (C) POC for percentage of infection of the Huh7.5 drug screen performed at 0.5 μM. 33 drugs had >60% reduction in infection with >80% cell viability. (D) Distribution of 23 validated antivirals by drug target class. (E) Dose-response analysis of the candidates with a selectivity index (SI) > 3 identified in the screen. Data represent the average of three independent experiments ± SD.

Article Snippet: High-throughput screening in human Huh7.5 cells to identify antivirals against SARS-CoV-2 (A) Huh7.5 cells were infected with SARS-CoV-2 (MOI = 1) and 30 hpi processed for microscopy. (B) Dose-response analysis of Huh7.5 cells treated with hydroxychloroquine or remdesivir.

Techniques: High Throughput Screening Assay, Infection, Microscopy

Journal: Cell Reports

Article Title: Drug repurposing screens reveal cell-type-specific entry pathways and FDA-approved drugs active against SARS-Cov-2

doi: 10.1016/j.celrep.2021.108959

Figure Lengend Snippet: Cell-type-specific dependencies of entry inhibitors (A) Calu-3 human lung epithelial cells were infected with SARS-CoV-2 (MOI = 0.5) and processed for microscopy 48 hpi. (B) Dose-response analysis of Calu-3 cells treated with quinolines or remdesivir. Data represent the average of four independent experiments ± SD. (C) IC 50 , CC50, and SI for Vero, Huh7.5, and Calu-3 cells treated with a panel of quinolines or remdesivir. Data represent the average of four independent experiments ± SD. (D) Dose-response analysis of Calu-3 cells treated with the cathepsin inhibitor Z-FA-FMK. Data represent the average of four independent experiments ± SD. (E) Dose response analysis of Calu-3, Vero, and Huh7.5 cells treated with camostat. Data represent the average of ≥2 independent experiments ± SD. (F) IC 50 , CC50, and SI for camostat across cell types. (G) Immunoblot of Vero, Huh7.5, and Calu-3 cells probed for Ace2 and tubulin as a loading control. Representative blot is shown. (H) qRT-PCR of Ace2 or TMPRSS2 comparing Huh7.5 and Calu-3 cells. Data represent the mean ± SEM for ≥2 independent experiments.

Article Snippet: High-throughput screening in human Huh7.5 cells to identify antivirals against SARS-CoV-2 (A) Huh7.5 cells were infected with SARS-CoV-2 (MOI = 1) and 30 hpi processed for microscopy. (B) Dose-response analysis of Huh7.5 cells treated with hydroxychloroquine or remdesivir.

Techniques: Infection, Microscopy, Western Blot, Quantitative RT-PCR

Journal: Cell Reports

Article Title: Drug repurposing screens reveal cell-type-specific entry pathways and FDA-approved drugs active against SARS-Cov-2

doi: 10.1016/j.celrep.2021.108959

Figure Lengend Snippet: Validation of antiviral activity of nine candidates in Calu-3 cells (A) Dose-response analysis of Huh7.5 candidate antivirals in Calu-3 cells with a SI > 3. Data represent the average of ≥4 independent experiments ± SD. (B) qRT-PCR analysis of nine candidate antivirals in Calu-3 cells. Data represent the mean ± SEM for ≥2 independent experiments.

Article Snippet: High-throughput screening in human Huh7.5 cells to identify antivirals against SARS-CoV-2 (A) Huh7.5 cells were infected with SARS-CoV-2 (MOI = 1) and 30 hpi processed for microscopy. (B) Dose-response analysis of Huh7.5 cells treated with hydroxychloroquine or remdesivir.

Techniques: Activity Assay, Quantitative RT-PCR

Journal: Cell Reports

Article Title: Drug repurposing screens reveal cell-type-specific entry pathways and FDA-approved drugs active against SARS-Cov-2

doi: 10.1016/j.celrep.2021.108959

Figure Lengend Snippet: Cyclosporine is antiviral against SARS-CoV-2 independent of calcineurin (A) Dose-response analysis of Huh7.5 cells treated with a panel of cyclosporins and related drugs. Data represent the average of ≥2 independent experiments ± SD. (B) Dose-response analysis of Calu-3 cells treated with a panel of cyclosporins and related drugs. Data represent the average of five independent experiments ± SD. (C) Dose-response analysis of Calu3 cells treated with cyclophilin-selective drugs NIM811 and alisporivir. Data represent the average of five independent experiments ± SD. (D) Table of IC 50 s, CC50s, and SI of Huh7.5 cells and Calu-3 cells treated with the indicated drugs. (E) qRT-PCR analysis of viral replication in Huh7.5 and Calu-3 cells treated with the indicated drugs. (F) qRT-PCR analysis of viral replication in iAT2 cells treated with the indicated drugs. (G) qRT-PCR of NHBE cells treated with the indicated drug. For (E)–(G), data represent the mean ± SEM for ≥2 independent experiments.

Article Snippet: High-throughput screening in human Huh7.5 cells to identify antivirals against SARS-CoV-2 (A) Huh7.5 cells were infected with SARS-CoV-2 (MOI = 1) and 30 hpi processed for microscopy. (B) Dose-response analysis of Huh7.5 cells treated with hydroxychloroquine or remdesivir.

Techniques: Quantitative RT-PCR

Journal: Cell Reports

Article Title: Drug repurposing screens reveal cell-type-specific entry pathways and FDA-approved drugs active against SARS-Cov-2

doi: 10.1016/j.celrep.2021.108959

Figure Lengend Snippet:

Article Snippet: High-throughput screening in human Huh7.5 cells to identify antivirals against SARS-CoV-2 (A) Huh7.5 cells were infected with SARS-CoV-2 (MOI = 1) and 30 hpi processed for microscopy. (B) Dose-response analysis of Huh7.5 cells treated with hydroxychloroquine or remdesivir.

Techniques: Recombinant, SYBR Green Assay, Software