Aspulvins A-H, Aspulvinone Analogues with SARS-CoV-2 M Inhibitory and Anti-inflammatory Activities from an Endophytic sp.

Eight new aspulvinone analogues, aspulvins A-H (-) and aspulvinones D, M, O, and R (-), were isolated from cultures of the endophytic fungus sp. 7951. Detailed spectroscopic analyses were conducted to determine the structures of the new compounds. All isolates displayed different degrees of inhibitory activity against the severe acute respiratory syndrome coronavirus 2 main protease (SARS-CoV-2 M) at 10 μM. Notably, compounds , , and showed potential SARS-CoV-2 M inhibition with IC values of 10.3 ± 0.6, 9.4 ± 0.6, and 7.7 ± 0.6 μM, respectively. For all compounds except and , the anti-inflammatory activity occurred by inhibiting the release of lactate dehydrogenase (LDH) with IC values ranging from 0.7 to 7.4 μM. Compound showed the most potent anti-inflammatory activity by inhibiting Casp-1 cleavage, IL-1β maturation, NLRP3 inflammasome activation, and pyroptosis. The findings reveal that the aspulvinone analogues , , and could be promising candidates for coronavirus disease 2019 (COVID-19) treatment as they inhibit SARS-CoV-2 infection and reduce inflammatory reactions caused by SARS-CoV-2.