Abstract
Eight new aspulvinone analogues, aspulvins A-H ( 1 – 8 ) and aspulvinones D, M, O, and R ( 9 – 12 ), were isolated from cultures of the endophytic fungus Cladosporium 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 pro ) at 10 μM. Notably, compounds 9 , 10 , and 12 showed potential SARS-CoV-2 M pro inhibition with IC 50 values of 10.3 ± 0.6, 9.4 ± 0.6, and 7.7 ± 0.6 μM, respectively. For all compounds except 3 and 4 , the anti-inflammatory activity occurred by inhibiting the release of lactate dehydrogenase (LDH) with IC 50 values ranging from 0.7 to 7.4 μM. Compound 10 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 9 , 10 , and 12 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.
【초록키워드】 COVID-19, Treatment, coronavirus disease, Structure, SARS-CoV-2, Coronavirus disease 2019, coronavirus, SARS-COV-2 infection, Infection, LDH, protease, severe acute respiratory syndrome Coronavirus, lactate dehydrogenase, anti-inflammatory activity, NLRP3 inflammasome, Culture, pyroptosis, cleavage, analogues, compounds, NLRP3, IL-1β, Lactate, structures, Candidates, acute respiratory syndrome, Activation, acute respiratory syndrome coronavirus, maturation, Compound, M pro, candidate, cultures, inflammatory reaction, inhibitory activity, inflammatory reactions, analogue, isolate, Casp, occurred, caused, conducted, determine, analysis, reduce, inhibiting, Cladosporium, inhibit SARS-CoV-2, 【제목키워드】 SARS-CoV-2, activity, M pro, analogue, Cladosporium,