Article Figures & Data
Figures
- FIG 1
Final positions of ATV and LPV on Mpro at the end of a molecular dynamics simulation. Representative images of LPV (A; blue structure) and ATV (B; orange structure) positioned in Mpro (green). Two-dimensional (2D) representation of the interactions of LPV (C) and ATV (D) in the Mpro active site at the end of 100-ns molecular dynamics simulation.
- FIG 2
Inhibition of proteinase activity through an analysis of gelatinolytic activity. Vero cells were mock treated or infected with SARS-CoV-2 at an MOI of 0.1 for 48 h before lysis and preparation of a cellular fraction. Fractions containing 12 μg of total protein were separated by electrophoresis followed by cutting the gels into their individual lanes that were incubated in 10 mM sodium acetate buffer (pH 5.5) in the absence (Nil) or presence of 10 μM E-64, ATV, or RTV. Gelatinolytic bands indicative of enzymatic activity were revealed by negative staining with amide black solution. Molecular mass markers are indicated.
- FIG 3
The antiviral activity of ATV and ATV/RTV against SARS-CoV-2. Vero (A and B) or A549 (C) cells were infected with SARS-CoV-2 at an MOI of 0.01 and exposed to the indicated concentrations of atazanavir (ATV), atazanavir/ritonavir (ATV/RTV; 3:1), chloroquine (CQ), remdesivir (RDV), or lopinavir/ritonavir (LPV/RTV; 4:1). After 2 days, viral replication in the culture supernatant was measured by TCID50/ml (A) or RT-PCR (B and C). The data represent means ± standard errors of the means (SEMs) from three independent experiments.
- FIG 4
ATV and ATV/RTV impair SARS-CoV-2 replication, cell death, and cytokine storms in human primary monocytes. Human primary monocytes were infected at an MOI of 0.01 and treated with the indicated concentrations of atazanavir (ATV), atazanavir/ritonavir (ATV/RTV; 3:1), chloroquine (CQ), remdesivir (RDV), or lopinavir/ritonavir (LPV/RTV; 4:1). After 24 h, cell-associated subgenomic RNA levels (A) and LDH release (B) as well as the levels of IL-6 (C) and TNF-α (D) were measured in the culture supernatant. The data represent means ± standard deviations (SDs) of experiments with cells from at least three healthy donors. *, P < 0.05 compared to untreated cells (Nil).
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