Figure 4
From: Discovery of SARS-CoV-2 antiviral synergy between remdesivir and approved drugs in human lung cells
Velpatasvir and elbasvir enhance remdesivir activity when used in their commercially available co-formulation with sofosbuvir and grazoprevir. All experiments shown are in Calu-3 cells infected with SARS-CoV-2. (a) Left panel: Two-dimensional representation of dose response interaction matrix. X-axis—Remdesivir (up to 10 μM), y-axis: Sofosbuvir (up to 40 μM). Color gradient indicates Inhibition of CPE (%); white–0%, red-100%. Middle panel: Topographic two-dimensional map of synergy scores determined in synergyfinder 34 from the data in (a), axes as in (b), color gradient indicates synergy score (red – highest score). NB coloring scheme and z-axis autoscales to the highest value observed, inflating small changes for weak compounds such as sofosbuvir. (b) As in (a), but remdesivir combined with velpatasvir (up to 10 μM); (c) as in (a) but remdesivir combined with both velpatasvir (up to 10 μM) and sofosbuvir (up to 40 μM); axis indicates sofosbuvir concentration only, Velpatasvir is 4 × lower. (d) Dose response of remdesivir alone (black) and in combination with 10 μM velpatasvir (red) or 10 μM velpatasvir/40 uM sofosbuvir (blue). (e) as in (a), but remdesivir combined with grazoprevir (up to 40 μM). (f) as in (a), but remdesivir combined with elbasvir (up to 40 μM). (g) as in (a), but remdesivir combined with both elbasvir and grazoprevir (both up to 40 μM). (h) Dose response of remdesivir alone (black) and in combination with 10 μM elbasvir (red) or 10uM elbasvir/10 μM grazoprevir (blue).
