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

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.

Exploring new catechin derivatives as SARS-CoV-2 Mpro inhibitors from tea by molecular networking, surface plasma resonance, enzyme inhibition, induced fit docking, and metadynamics simulations

“…After 10 min of incubation, the relative fluorescence unit (RFU) was read on a microplate reader (DU-730; Beckman Coulter, Brea, CA, USA) at the excitation of 340 nm and the emission of 490 nm. The calculation formula for inhibition rate is consistent with the previous report [ 25 ].…”

“…Liang et al have discovered the aspulvinone analogs as the potential inhibitors using a beyotime enhanced inhibition kit. The IC 50 values of aspulvinones D, M, and R are 10.3 ± 0.6, 9.4 ± 0.6, and 7.7 ± 0.6 μM, respectively [ 25 ]. In the previous reports, the IC 50 of ebselen was different from different reports such as 0.67 ± 0.09 μM [ 4 ] and 0.04 ± 0.004 μM [ 20 ].…”

Microbial Natural Products with Antiviral Activities, Including Anti-SARS-CoV-2: A Review

“…Previously, the fungus was isolated from Paris polyphylla var. yunnanensis, a medicinal plant collected in Kunming, China [154].…”

“…M pro plays an essential role in the replication and transcription of SARS-CoV-2. There are a number of microbe-produced natural products with the ability to inhibit M pro , including aurasperone A [152]; neoechinulin A [153]; as well as aspulvinone D, M, and R [154].…”

Collective synthesis of aspulvinone and its analogues by vinylogous aldol condensation of substituted tetronic acids with aldehydes

“…6 Recently, a study showed that some aspulvinones could inhibit SARS-CoV-2 infection and reduce inammatory reactions caused by SARS-CoV-2. 7 As part of our work, aspulvinone O and H were isolated from the rice culture of Aspergillus terreus and identied as potent bioactive inhibitors of GOT1 and novel anti-tumor agents for PDAC therapy. 8,9 However, the poor isolated yield and limited structure variation restricted our further study of their pharmaceutical properties.…”