Fig. 4: Restoration of 1,5-AG reduced SARS-CoV-2 infection and prevented the lung pathology in db/db mice.

a,b, Metabolic kinetics of 1,5-AG in serum (a) and lung (b) of mice implanted with osmotic pumps (n = 4 mice). P = 0.001 and P = 0.0102 for control PBS versus db/db PBS at day 12 of serum and lung. P = 0.0056, P = 0.0006 and P = 0.0002 for db/db PBS versus db/db 1,5-AG at day 4, 8 and 12 of serum. P = 0.0472, P = 0.001 and P = 0.0114 for db/db PBS versus db/db 1,5-AG at day 4, 8 and 12 of lung. ^****P < 0.0001. c, The weight change of infected mice. Gray P values, control PBS versus db/db PBS. Orange P values, db/db PBS versus db/db 1,5-AG. P = 0.0057, P = 0.0140, P = 0.0009, P = 0.0320 and P = 0.0111 for control PBS versus db/db PBS at day 1, 4, 5, 6 and 7. P = 0.0374, P = 0.0076 and P = 0.0004 for db/db PBS versus db/db 1,5-AG at day 5, 6 and 7. d–f, SARS-CoV-2 loads in the lung (d), trachea (e) and nasal turbinate (f) of infected mice. Each dot represents one mouse (n = 6 control PBS, n = 8 db/db PBS and n = 8 db/db 1,5-AG, male:female, 1:1). P = 0.0073, P = 0.0096 and P = 0.0432 for control PBS versus db/db PBS of lung, trachea and nasal turbinate. P < 0.0001, P = 0.0006 and P = 0.0011 for db/db PBS versus db/db 1,5-AG of lung, trachea and nasal turbinate. g, Immunofluorescence staining of lungs. A representative of three images from three biological replicates is shown. Scale bars, 500 μm (red), 100 μm (white) and 20 μm (orange). h, Histopathology of lungs. Red frame, lymphocyte infiltration; triangle, interstitial congestion; blue frame, protein accumulation. A representative of three images from three biological replicates is shown. Scale bars, 100 μm (black), 10 μm (red). i, Reduction of serum 1,5-AG is associated with clinical COVID-19 severity. One dot represents one patient (n = 64 healthy controls, n = 79 nonsevere patients and n = 71 severe patients). Data were analyzed using a nonparametric two-sided Mann–Whitney U-test and adjusted using a Dunnett’s test (a–f,i). ^*P < 0.05; ^**P < 0.01; ^***P < 0.001; and ^****P < 0.0001. Data are mean ± s.e.m. (a–c). The horizontal line is the median value (d–f,i). Experiments were performed independently at least three biological replicates with comparable results (c–h).

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