Fig. 5
From: Therapeutic strategy targeting host lipolysis limits infection by SARS-CoV-2 and influenza A virus
In vivo antiviral and anti-proinflammatory cytokine effects of lipase inhibitors against influenza A virus (IAV) and SARS-CoV-2. a Scheme of chemical administration twice daily for 4 consecutive days after challenge with 103 PFU of mouse-adapted IAV PR8 strain to mice (n = 16). b, c Survival rates (expressed as percentages) of IAV-challenged mice by treatment with either atglistatin (b) or CAY10499 (c). d Scheme of chemical administration twice daily for 4.5 consecutive days after challenge with 105 TCID50 of SARS-CoV-2 KCDC03 strain to Syrian hamsters (n = 5). e Reduction in SARS-CoV-2-induced gross lung lesions in hamsters by treatment with atglistatin. f In vivo inhibition of FFA and glycerol release from LDs in lungs sampled from SARS-CoV-2-challenged hamsters (n = 5) by treatment with atglistatin. g, h Reduction in SARS-CoV-2 genome copy number and infectious progeny production in lungs sampled from SARS-CoV-2-challenged hamsters (n = 5) by treatment with atglistatin. i Representative images of LDs and virus replication. Retention of LDs (green, lower panels) and inhibition of SARS-CoV-2 replication (red, middle panels) in alveolar epithelial cells of lung tissues sampled from SARS-CoV-2-challenged hamsters by treatment with atglistatin. j Representative images of histological lung lesions. Amelioration of histological lung lesions (upper panels) and inhibition of SARS-CoV-2 replication (lower panels) by treatment with atglistatin. k–o The graphical representation of the IFN-α, IFN-β, IL-6, TNF-α, and MCP-1 levels in bronchoalveolar lavage fluids (BALFs) sampled from SARS-CoV-2-challenged hamsters or IAV-challenged mice, which were vehicle-treated or treated with atglistatin or CAY10499. Each cytokine in BALFs was determined by ELISA assay as described in Supplementary Information. Results are presented as arithmetic means ± SD. *P < 0.05; **P < 0.01; ***P < 0.001, ****P < 0.0001, one-way analysis of variance with Tukey’s correction for multiple comparisons. Scale bars = 30 µm for panel i and 200 µm for panel j
