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

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 (Mpro). 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.

Anti-Inflammatory, Antiallergic, and COVID-19 Main Protease (Mpro) Inhibitory Activities of Butenolides from a Marine-Derived Fungus Aspergillus terreus.

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.

Identifying the specific-targeted marine cerebrosides against SARS-CoV-2: an integrated computational approach.

Cerebrosides are a group of metabolites belonging to the glycosphingolipids class of natural products. So far, 167 cerebrosides, compounds 1-167, have been isolated from diverse marine organisms or microorganisms. The as yet smaller number of compounds that have been studied more in depth proves a potential against challenging diseases, such as cancer, a range of viral and bacterial diseases, as well as inflammation. This review provides a comprehensive summary on this so far under-explored class of compounds, their chemical structures, bioactivities, and their marine sources, with a full coverage to the end of 2020. Today, the global pandemic concern, COVID-19, has claimed millions of death cases around the world, making the development of anti-SARS-CoV-2 drugs urgently needed for such a battle. Accordingly, selected examples from all subclasses of cerebrosides were virtually screened for potential inhibition of SARS-CoV-2 proteins that are crucially involved in the viral-host interaction, viral replication, or in disease progression. The results highlight five cerebrosides that could preferentially bind to the hACE2 protein, with binding scores between -7.1 and -7.6 kcal mol-1 and with the docking poses determined underneath the first α1-helix of the protein. Moreover, the molecular interaction determined by molecular dynamic (MD) simulation revealed that renieroside C1 (60) is more conveniently involved in key hydrophobic interactions with the best stability, least deviation, least ΔG (-6.9 kcal mol-1) and an RMSD value of 3.6 Å. Thus, the structural insights assure better binding affinity and favorable molecular interaction of renieroside C1 (60) towards the hACE2 protein, which plays a crucial role in the biology and pathogenesis of SARS-CoV-2.

Natural coumarins as potential anti-SARS-CoV-2 agents supported by docking analysis.

COVID-19 is a global pandemic first identified in China, causing severe acute respiratory syndrome. One of the therapeutic strategies for combating viral infections is the search for viral spike proteins as attachment inhibitors among natural compounds using molecular docking. This review aims at shedding light on the antiviral potential of natural products belonging to the natural-products class of coumarins up to 2020. Moreover, all these compounds were filtered based on ADME analysis to determine their physicochemical properties, and the best 74 compounds were selected. Using virtual-screening methods, the selected compounds were investigated for potential inhibition of viral main protease (Mpro), viral methyltransferase (nsp16/10 complex), viral recognition binding domain (RBD) of S-protein, and human angiotensin-converting enzyme 2 (ACE2), which is the human receptor for viral S-protein targets, using molecular-docking studies. Promising potential results against SARS-CoV-2 RNA-dependent RNA polymerase (RdRp) and methyltransferase (nsp16) are presented.