Journal: Communications Biology

Article Title: PIKfyve-specific inhibitors restrict replication of multiple coronaviruses in vitro but not in a murine model of COVID-19

doi: 10.1038/s42003-022-03766-2

Figure Lengend Snippet: a Groups of mice were treated intraperitoneally with PIKfyve inhibitors WX8 or NDF once daily beginning 1 day pre-intranasal-challenge with 1 × 10 5 plaque forming units SARS-CoV-2 (B.1.351). EIDD-2801 dosed twice a day was used as a positive treatment control and uninfected treatment controls were included to assess cytotoxicity. Image created using BioRender. b Weight changes were determined for 4 days post-challenge, plotted as the group mean with error bars indicating the ±SD. c Infectious viral loads from lung homogenates at 2 (black) or 4 (gray) days post SARS-CoV-2 challenge. d Lungs were collected at 2- or 4-days post-challenge and stained with hematoxylin and eosin to assess bronchiolar and alveolar damage and immune cell infiltration (500-μm scale bar shown at bottom left, representative for all panels). Mixed-effects analysis was used to compare differences in weight change or viral loads from lung homogenates between infection treatment groups and the vehicle-treated control group; ** p ≤ 0.01, **** p ≤ 0.0001. dpi, days post-infection; PO, oral dosing; IP, intraperitoneal; IN, intranasal.

Article Snippet: EIDD-2801 (150 mg/kg, WuXi AppTec) was dosed orally, twice daily, starting one day prior to infection was used as a positive control for all experiments, as it has been shown to be efficacious in animal models previously , .

Techniques: Staining, Infection

Journal: Communications Biology

Article Title: PIKfyve-specific inhibitors restrict replication of multiple coronaviruses in vitro but not in a murine model of COVID-19

doi: 10.1038/s42003-022-03766-2

Figure Lengend Snippet: a Groups of mice were treated intraperitoneally with PIKfyve inhibitors Apilimod, WX8, or NDF once daily beginning 1 day post-intranasal-challenge with 1 × 10 3 plaque forming units SARS-CoV-2 (MA-10). EIDD-2801 dosed twice a day was used as a positive treatment control and uninfected treatment controls were included to assess cytotoxicity. Image created using Biorender. b Weight changes were determined for 4 days post-challenge, plotted as the group mean with error bars indicating the ±SD. c Infectious viral loads from lung homogenates at 2- (black) or 4- (gray) days post SARS-CoV-2 challenge. d Survival curves for treatment groups. e Lungs were collected at 2- or 4-days post-challenge and stained with hematoxylin and eosin to assess bronchiolar and alveolar damage and immune cell infiltration (500-μm scale bar shown at bottom left, representative for all panels). Mixed-effects analysis was used to compare differences in weight change or viral loads from lung homogenates between infection treatment groups and the vehicle-treated control group; * p ≤ 0.1, *** p ≤ 0.001, **** p ≤ 0.0001. dpi, days post-infection; PO, oral dosing; IP, intraperitoneal; IN, intranasal.

Article Snippet: EIDD-2801 (150 mg/kg, WuXi AppTec) was dosed orally, twice daily, starting one day prior to infection was used as a positive control for all experiments, as it has been shown to be efficacious in animal models previously , .

Techniques: Staining, Infection

Journal: Frontiers in Pharmacology

Article Title: Preclinical Pharmacokinetics and In Vitro Properties of GS-441524, a Potential Oral Drug Candidate for COVID-19 Treatment

doi: 10.3389/fphar.2022.918083

Figure Lengend Snippet: Anti-SARS-CoV-2 activity of GS-441524 and Remdesivir. (A) GS-441524 inhibited SARS-CoV-2 CPE in Vero E6 cells with an EC 50 of 1.86 μM compared to remdesivir (EC 50 of 7.43 μM). Neither compounds showed cytotoxicity at the concentrations used. (B) GS-441524 reduced viral load of SARS-CoV-2 infection in the 3D EpiAirway HAE tissue model. TCID50/mL was determined for remdesivir, GS-441524 and EIDD-2801 after (B) 24 h or (C) 96 h of SARS-CoV-2 infection. All graphs show mean ± standard error of the mean (SEM).

Article Snippet: For Vero E6 CPE assay and EpiAirway efficacy study, GS-441524 and remdesivir were purchased from MedChem Express (Monmouth Junction, NJ), and EIDD-2801 was purchased from Cayman Chemical (Ann Arbor, MI).

Techniques: Activity Assay, Infection