New meroterpenoids and polyketides from the endophytic fungus Paraphaeosphaeria sp. C-XB-J-1 and their anti-inflammatory and SARS-CoV-2 M pro inhibitory activities

Seven new meroterpenoids, paraphaeones A -G ( 1 - 7 ), and two new polyketides, paraphaeones H -I ( 8 - 9 ), along with eight known compounds ( 10 - 17 ), were isolated from the endophytic fungus Paraphaeosphaeria sp. C-XB-J-1. The structures of 1 - 9 were identified through the analysis of 1 H, 13 C, and 2D NMR spectra, assisted by HR-ESIMS data. Compounds 1 and 7 exhibited a dose -dependent decrease in lactate dehydrogenase levels, with IC 50 values of 1.78 mu M and 1.54 mu M, respectively. Moreover, they inhibited the secretion of IL-1 beta and CASP-1, resulting in a reduction in the activity levels of NLRP3 inflammasomes. Fluorescence microscopy results indicated that compound 7 concentration -dependently attenuated cell pyroptosis. Additionally, compounds 4 and 7 showed potential inhibitory effects on the severe acute respiratory syndrome coronavirus-2 main protease (SARSCoV-2 M pro ), with IC 50 values of 10.8 +/- 0.9 mu M and 12.9 +/- 0.7 mu M, respectively.