ABSTRACT
In December 2020, the U.K. authorities reported to the World Health Organization (WHO) that a new COVID-19 variant, considered to be a variant under investigation from December 2020 (VUI-202012/01), was identified through viral genomic sequencing. Although several other mutants were previously reported, VUI-202012/01 proved to be about 70% more transmissible. Hence, the usefulness and effectiveness of the newly U.S. Food and Drug Administration (FDA)-approved COVID-19 vaccines against these new variants are doubtfully questioned. As a result of these unexpected mutants from COVID-19 and due to lack of time, much research interest is directed toward assessing secondary metabolites as potential candidates for developing lead pharmaceuticals. In this study, a marine-derived fungus Aspergillus terreus was investigated, affording two butenolide derivatives, butyrolactones I (1) and III (2), a meroterpenoid, terretonin (3), and 4-hydroxy-3-(3-methylbut-2-enyl)benzaldehyde (4). Chemical structures were unambiguously determined based on mass spectrometry and extensive 1D/2D NMR analyses experiments. Compounds (1-4) were assessed for their in vitro anti-inflammatory, antiallergic, and in silico COVID-19 main protease (Mpro) and elastase inhibitory activities. Among the tested compounds, only 1 revealed significant activities comparable to or even more potent than respective standard drugs, which makes butyrolactone I (1) a potential lead entity for developing a new remedy to treat and/or control the currently devastating and deadly effects of COVID-19 pandemic and elastase-related inflammatory complications.
Subject(s)
4-Butyrolactone/analogs & derivatives , Anti-Allergic Agents/chemistry , Anti-Inflammatory Agents/chemistry , Aspergillus/chemistry , SARS-CoV-2/enzymology , Viral Matrix Proteins/antagonists & inhibitors , 4-Butyrolactone/chemistry , 4-Butyrolactone/isolation & purification , 4-Butyrolactone/metabolism , Anti-Allergic Agents/metabolism , Anti-Inflammatory Agents/metabolism , Aspergillus/growth & development , Aspergillus/metabolism , Binding Sites , COVID-19/pathology , COVID-19/virology , Catalytic Domain , Humans , Leukocyte Elastase/antagonists & inhibitors , Leukocyte Elastase/metabolism , Magnetic Resonance Spectroscopy , Molecular Conformation , Molecular Docking Simulation , Neutrophils/enzymology , SARS-CoV-2/isolation & purification , Seawater/microbiology , Viral Matrix Proteins/metabolismABSTRACT
The latest chapter of the historic battle of humans against pathogenic microbes is the severe acute respiratory syndrome (SARS)-like coronavirus-2 (SARS-CoV-2), responsible for COVID-19, a respiratory disease declared a global pandemic by the WHO on March 11, 2020 [...].