The COVID-19 pandemic caused by the novel SARS-CoV-2 virus has caused havoc across the entire world. Even though several COVID-19 vaccines are currently in distribution worldwide, with others in the pipeline, treatment modalities lag behind. Accordingly, researchers have been working hard to understand the nature of the virus, its mutant strains, and the pathogenesis of the disease in order to uncover possible drug targets and effective therapeutic agents. As the research continues, we now know the genome structure, epidemiological and clinical features, and pathogenic mechanism of SARS-CoV-2. Here, we summarized the potential therapeutic targets involved in the life cycle of the virus. On the basis of these targets, small-molecule prophylactic and therapeutic agents have been or are being developed for prevention and treatment of SARS-CoV-2 infection.
Free radical-scavenging activity of isoflavones and some isoflavone metabolites have been described previously, but the results are inconsistent. The objective of the present study was to find out the pivotal factors that influence an accurate detection of both superoxide anion and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity. We here showed for the first time that organic solvents, including methanol, ethanol and acetone, were of strong superoxide radical-scavenging activity at concentrations down to 0.1% (v/v), however, no such activity was observed with acetonitrile at concentrations up to 2.0% (v/v). In DPPH assay, we found that the DPPH radical-scavenging ratio increased together with the extended reaction time. Based on our findings, improved in vitro assays for the detection of radical-scavenging activity of both isoflavones (daidzein and genistein) and isoflavone metabolites, including dihydrodaidzein (DHD), dihydrogenistein (DHG), and O-desmethylangolensin (O-Dma), were established.
Arctium lappa L. (A. lappa) is a popularly used vegetable as well as herbal medicine. Human intestinal microflora was reported to convert arctiin, the lignan compound with highest content in the dried fruits of Arctium lappa, to a series of metabolites. However, the specific bacterium responsible for the formation of 3'-desmethylarctigenin (3'-DMAG), the most predominant metabolite of arctiin by rat or human intestinal microflora, has not been isolated yet. In the present study, we isolated one single bacterium, which we named Blautia sp. AUH-JLD56, capable of solely biotransforming arctiin or arctigenin to (-)-3'-DMAG. The structure of the metabolite 3'-DMAG was elucidated by electrospray ionization mass spectrometry (ESI-MS) and (1)H and (13)C nuclear magnetic resonance spectroscopy. The biotransforming kinetics and maximum biotransforming capacity of strain AUH-JLD56 was investigated. In addition, the metabolite 3'-DMAG showed significantly higher 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical-scavenging activity than that of the substrate arctigenin at the concentrations tested.
Soy isoflavone metabolites, which are more biologically active than their precursor isoflavones, are currently receiving much more attention. However, the non-natural isoflavone metabolites are synthesized or biosynthesized under obligate anaerobic conditions. Here, we describe a new approach to the reduction of soy isoflavones daidzein and genistein under aerobic conditions by use of the recombinant Escherichia coli whole-cell expressing isoflavone reductase. Our study provides the first evidence that isoflavone metabolites, such as dihydrodaidzein and dihydrogenistein, are able to be produced efficiently under aerobic conditions.
Arctiin is the most abundant bioactive compound contained in the Arctium lappa plant. In our previous study, we isolated one single bacterium capable of bioconverting arctigenin, an aglycone of arctiin, to 3'-desmethylarctigenin (3'-DMAG) solely. However, to date, a specific bacterium capable of producing other arctiin metabolites has not been reported. In this study, we isolated one single bacterium, which we named Eggerthella sp. AUH-JLD49s, capable of bioconverting 3'-DMAG under anaerobic conditions. The metabolite of 3'-DMAG by strain AUH-JLD49s was identified as 3'-desmethyl-4'-dehydroxyarctigenin (DMDH-AG) based on electrospray ionization mass spectrometry (ESI-MS) and H andC nuclear magnetic resonance spectroscopy. The bioconversion kinetics and bioconversion capacity of strain AUH-JLD49s were investigated. In addition, the metabolite DMDH-AG showed an inhibitory effect on cell growth of human colon cancer cell line HCT116 and human breast cancer cell line MDA-MB-231.
Due to the high sugar content of Mopan persimmon, which has an annual output of more than 0.5 million tons in China, it can be processed to make fruit wine. In this study, a strain of yeast screened from different persimmon samples was used for persimmon wine fermentation. The optimal conditions of persimmon wine fermentation were determined through single-factor experiments as follows: Yeast addition of 0.08 g/kg; a fermentation temperature of 28 °C; sucrose addition of 18%; and pectinase addition of 0.01%. Under these conditions, the alcohol content of persimmon wine reached 12.9%. The addition of pectinase during persimmon wine fermentation was found to decompose pectin at high speed, reduce the viscosity of the fermentation liquid, increase the dissolved oxygen content in the fermentation liquid, promote the growth and reproduction of yeast, and effectively convert the sugars into alcohol. After fermentation, alcohol, residual sugars, and total phenolic content with or without pectinase treatment were 12.9 and 4.4%, 2.2 and 13.4 g/L, and 738.7 and 302 µg/mL, respectively. Scanning electron microscopy (SEM) results showed that compared with the mash without pectinase treatment, the mash with pectinase had a larger network structure and more pores and yeasts.
Strain Aeroto-AUH-JLC108 is the first reported pure culture responsible for the formation of O-Dma from daidzein in the presence of atmospheric oxygen.
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