Journal: JCI insight

Article Title: Sangivamycin is highly effective against SARS-CoV-2 in vitro and has favorable drug properties.

doi: 10.1172/jci.insight.153165

Figure Lengend Snippet: Figure 1. Sangivamycin inhibits SARS-CoV-2 replication in multiple cell types. (A–C) High-content imaging assays were performed to determine compound potency (blue line), and CellTiter-Glo assays were performed to determine cell viability (red line) of sangivamycin-pretreated cells exposed to SARS-CoV-2. Results are reported as percentage inhibition (blue values) and cytotoxicity (red values) relative to untreated controls. Error bars represent standard deviations (SDs) from tests run for each concentration in triplicate on 3 plates for Vero E6 and Calu-3 (n = 9) and sextuplet on 4 plates for Caco-2 (n = 24). IC50, half-maximal inhibitory concentration (lower dotted line); IC90, 90% inhibitory concentration (upper dotted line); CC50, half-maximal cytotoxic concentration (lower dotted line); SI (bottom right), selectivity index (CC50/IC50). ±, standard error of the mean (SEM) across plates (n = 3 for Vero E6 and Calu-3, n = 4 for Caco-2).

Article Snippet: One experiment resulted in S/R constant dose ratios of 1:5, 1:10, 1:20, 1:30, and 1:40, with a sangivamycin concentration range of 1.5–300 nM and remdesivir concentrations of 46–6000 nM; the second experiment resulted in S/R constant ratios of 1:100, 1:133, and 1:200, with sangivamycin concentrations of 1.5–100 nM and remdesivir concentrations of 313–10,000 nM.

Techniques: Imaging, Inhibition, Concentration Assay

Journal: JCI insight

Article Title: Sangivamycin is highly effective against SARS-CoV-2 in vitro and has favorable drug properties.

doi: 10.1172/jci.insight.153165

Figure Lengend Snippet: Figure 2. Sangivamycin is a more potent antiviral against SARS-CoV-2 than remdesivir in multiple cell types in vitro. (A–C) Sangivamycin’s antiviral activity (Figure 1) compared with remdesivir using identical SARS-CoV-2 MOIs and sampling time points. Results are reported as percentage inhibition rel- ative to untreated controls (blue values for sangivamycin, yellow values for remdesivir). Error bars represent SDs for sangivamycin as described in Figure 1, and for remdesivir each concentration was run in triplicate on 3 plates for Vero E6 and Calu-3 (n = 9) and triplicate on 4 plates for Caco-2 (n = 12). IC50, half-maximal inhibitory concentration (lower dotted line); IC90, 90% inhibitory concentration (upper dotted line).

Article Snippet: One experiment resulted in S/R constant dose ratios of 1:5, 1:10, 1:20, 1:30, and 1:40, with a sangivamycin concentration range of 1.5–300 nM and remdesivir concentrations of 46–6000 nM; the second experiment resulted in S/R constant ratios of 1:100, 1:133, and 1:200, with sangivamycin concentrations of 1.5–100 nM and remdesivir concentrations of 313–10,000 nM.

Techniques: In Vitro, Activity Assay, Sampling, Inhibition, Concentration Assay

Journal: JCI insight

Article Title: Sangivamycin is highly effective against SARS-CoV-2 in vitro and has favorable drug properties.

doi: 10.1172/jci.insight.153165

Figure Lengend Snippet: Figure 3. Sangivamycin is more potent against the Delta variant of SARS-CoV-2 than remdesivir. Sangivamycin’s antiviral activity compared with remdesivir using SARS-CoV-2 MOIs and sampling time points as detailed in Table 1 for SARS-CoV-2 variant B.1.617.2 (Delta) in Vero E6/TMPRSS2 (A) and Calu-3 (B) cells. Results are reported as percentage inhibition relative to untreated controls (blue values for sangivamycin, yellow values for remdesivir). Each dose was run in triplicate with error bars representing SDs. IC50, half-maximal inhibitory concentration (lower dotted line); IC90, 90% inhibitory concentration (upper dotted line).

Article Snippet: One experiment resulted in S/R constant dose ratios of 1:5, 1:10, 1:20, 1:30, and 1:40, with a sangivamycin concentration range of 1.5–300 nM and remdesivir concentrations of 46–6000 nM; the second experiment resulted in S/R constant ratios of 1:100, 1:133, and 1:200, with sangivamycin concentrations of 1.5–100 nM and remdesivir concentrations of 313–10,000 nM.

Techniques: Variant Assay, Activity Assay, Sampling, Inhibition, Concentration Assay

Journal: JCI insight

Article Title: Sangivamycin is highly effective against SARS-CoV-2 in vitro and has favorable drug properties.

doi: 10.1172/jci.insight.153165

Figure Lengend Snippet: Figure 4. Combining sangivamycin and remdesivir results in an additive effect against SARS-CoV-2 in multiple cell types. Constant ratios of sangivamycin to remdesivir (S:R) were used to evaluate combination effect against SARS-CoV-2 infection in Vero E6 cells and plotted relative to (A) sangivamycin concentration and (B) remdesivir concentration. Each dose combination was run in triplicate with error bars representing standard devi- ations (SDs). (C) Effects of different combinations of sangivamycin-to-remdesivir ratios on viral infection rate, fit to the Loewe interaction model. Isobologram showing ratio pairs that resulted in 50% virus inhibition calculated from the curves in A and B plotted on the y axis (values from A) and x axis (values from B) relative to the additive (dotted) line drawn between the IC50 values for sangivamycin (S:R = 1:0) and remdesivir (S:R = 0:1) alone. The results of experiments similar to those shown in A and B performed on Caco-2 and Calu-3 cells are shown in Supplemental Figure 3. (D and E) Isobolograms as in C calculated based on results in Supplemental Figure 3. The CI heatmap legend indicates color coding for S:R antagonism (red), additive efficacy (black), or synergy (green) based on ref. 23. CI, combination index.

Article Snippet: One experiment resulted in S/R constant dose ratios of 1:5, 1:10, 1:20, 1:30, and 1:40, with a sangivamycin concentration range of 1.5–300 nM and remdesivir concentrations of 46–6000 nM; the second experiment resulted in S/R constant ratios of 1:100, 1:133, and 1:200, with sangivamycin concentrations of 1.5–100 nM and remdesivir concentrations of 313–10,000 nM.

Techniques: Infection, Concentration Assay, Virus, Inhibition