Anti-Inflammatory, Antiallergic and COVID-19 Main Protease (M-pro) Inhibitory Activities of Butenolides from a Marine-Derived Fungus Aspergillus costaricaensis

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Abstract Amid the current COVID‐19 pandemic, the emergence of several variants in a relatively high mutation rate (twice per month) strengthened the importance of finding out a chemical entity that can be potential for developing an effective medicine. In this study, we explored ethyl acetate (EtOAc) extract of a marine‐derived fungus Aspergillus cosatricaensis afforded three butenolide derivatives, butyrolactones I, VI and V ( 1 – 3 ), two naphtho‐ γ ‐pyrones, TMC‐256 A1 ( 4 ) and rubrofusarin B ( 5 ) and methyl p ‐hydroxyphenyl acetate ( 6 ). Structure identification was unambiguously determined based on exhaustive spectral analyses including 1D/2D NMR and mass spectrometry. The isolated compounds ( 1 – 6 ) were assessed for their in vitro anti‐inflammatory, antiallergic, elastase inhibitory activities and in silico SARS‐CoV‐2 main protease (M pro ). Results exhibited that only butenolides ( 1 and 2 ) revealed potent activities similar to or more than reference drugs unlike butyrolactone V ( 3 ) suggesting them as plausible chemical entities for developing lead molecules.