Fig. 3: Absence of PLA₂G2D or PTGDR expression, or blocking PGD₂/PTGDR signalling, inhibits SARS2-N501Y_MA30 infection in vivo.

a, Weight (left) and survival (right) of middle-aged WT (n = 8), Ptgdr^−/− (n = 9) or Pla2g2d^−/− (n = 9) C57BL/6 mice infected with 5,000 PFUs of SARS2-N501Y_MA30. b, Viral titres in lungs at 2 (n = 7) and 5 dpi (n = 7). P values were determined by a log-rank (Mantel–Cox) test (a) and a two-tailed Student’s t-test (b). P < 0.0001, Pla2g2d^−/− versus WT; not significant, Ptgdr^−/− versus WT (a). P < 0.0001, Pla2g2d^−/− versus WT, 2 dpi; P < 0.0001, Ptgdr^−/− versus WT and Pla2g2d^−/− versus WT, 5 dpi (b). c, Lungs at 5 dpi from WT mice exhibited edema (marked with asterisks) and cellular infiltration/interstitial thickening whereas these were significantly reduced in lungs from Ptgdr^−/− or Pla2g2d^−/− mice. H&E stain. Scale bar, 40 μm. d, Summary scores (n = 6 for WT; n = 6 for Ptgdr^−/−; n = 8 for Pla2g2d^−/−). P values were determined by two-tailed Student’s t-test. P = 0.03, Ptgdr^−/− versus WT and P = 0.0007, Pla2g2d^−/− versus WT, edema/HM; P = 0.004, Pla2g2d^−/− versus WT, interstitial disease. e, Asapiprant structure. f, Experimental design for g and k. Vehicle or asapiprant was administered orally at 2–8 dpi to middle-aged (g–j) or young (k) C57BL/6 mice infected intranasally with SARS2-N501Y_MA30. g, Weight (left) and survival (right) of vehicle-treated (n = 10) or asapiprant-treated (n = 12) middle-aged mice. The P value was determined by a two-tailed Student’s t-test. P < 0.0001, asapiprant-treated versus vehicle-treated group. h, Lung viral titres of vehicle-treated (n = 8) or asapiprant-treated (n = 8) middle-aged mice at 5 dpi. The P value was determined by a two-tailed Student’s t-test. P < 0.0001, asapiprant-treated versus vehicle-treated group. i, The vehicle-treated group exhibited edema (asterisks) with occasional hyaline membranes (arrows), which were uncommon in asapiprant-treated mice at 5 dpi; H&E stain. Scale bar, 20 μm. j, Summary scores (n = 8 for vehicle-treated mice; n = 9 for asapiprant-treated mice). P values were determined by two-tailed Student’s t-test. P = 0.002, asapiprant-treated versus vehicle-treated group, edema/HM; P = 0.0002, asapiprant-treated versus vehicle-treated group, interstitial disease. HM, hyaline membranes. k, Weight (left) and survival (right) of vehicle-treated (n = 4) or asapiprant-treated (n = 4) young C57BL/6 mice infected with 5,000 PFUs of SARS2-N501Y_MA30. Data in a, d, g (left), j and k (left) are mean ± s.e.m. Data in b and h are geometric mean ± s.d.

Source data.