The coronavirus disease (COVID-19) caused by SARS-CoV-2 is creating tremendous human suffering. To date, no effective drug is available to directly treat the disease. In a search for a drug against COVID-19, we have performed a high-throughput X-ray crystallographic screen of two repurposing drug libraries against the SARS-CoV-2 main protease (Mpro), which is essential for viral replication. In contrast to commonly applied X-ray fragment screening experiments with molecules of low complexity, our screen tested already approved drugs and drugs in clinical trials. From the three-dimensional protein structures, we identified 37 compounds that bind to Mpro. In subsequent cell-based viral reduction assays, one peptidomimetic and six non-peptidic compounds showed antiviral activity at non-toxic concentrations. We identified two allosteric binding sites representing attractive targets for drug development against SARS-CoV-2.

The effect of solvent polarity on extraction yield and antioxidant properties of phytochemical compounds in bean seeds was studied. Seed flour of three varieties of bean was extracted in a series of organic solvents with increasing polarity (n-hexane, petroleum ether, chloroform, ethyl acetate, ethanol, acetone and water). Preliminary screening of phytochemicals showed the presence of tannins, flavonoids, cardiac glycosides, anthocyanins, terpenoids, carotenoids, ascorbic acid and reducing compounds in all extracts. One way analysis of variance (ANOVA) of results showed that extraction yield, phytochemical content and antioxidant properties were significantly influenced (p<0.05) by the polarity of extracting solvents. The regression analysis of data showed polarity-dependent second order polynomial variations in the extraction yield, phytochemical contents, antioxidant activity, reducing properties and free radical scavenging activity of each variety. Extraction in highly polar solvents resulted in high extract yield but low phenolic and flavonoid content as compared to non-polar ones. The polarity-dependent increase in total antioxidant activity and reducing properties indicates the extraction of strong antioxidant compounds in polar solvents. The study suggests the use of a combination of polar and nonpolar solvents to increase the extraction efficiency of phytochemicals with good antioxidant quality from the bean and other legume seeds.

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Oxidative stress and energy imbalance strongly correlate in neurodegenerative diseases. Repeated concussion is becoming a serious public health issue with uncontrollable adverse effects in the human population, which involve cognitive dysfunction and even permanent disability. Here, we demonstrate that traumatic brain injury (TBI) evokes oxidative stress, disrupts brain energy homeostasis, and boosts neuroinflammation, which further contributes to neuronal degeneration and cognitive dysfunction in the mouse brain. We also demonstrate that melatonin (an anti-oxidant agent) treatment exerts neuroprotective effects, while overcoming oxidative stress and energy depletion and reducing neuroinflammation and neurodegeneration. Male C57BL/6N mice were used as a model for repetitive mild traumatic brain injury (rmTBI) and were treated with melatonin. Protein expressions were examined via Western blot analysis, immunofluorescence, and ELISA; meanwhile, behavior analysis was performed through a Morris water maze test, and Y-maze and beam-walking tests. We found elevated oxidative stress, depressed phospho-5′AMP-activated protein kinase (p-AMPK) and phospho- CAMP-response element-binding (p-CREB) levels, and elevated p-NF-κB in rmTBI mouse brains, while melatonin treatment significantly regulated p-AMPK, p-CREB, and p-NF-κB in the rmTBI mouse brain. Furthermore, rmTBI mouse brains showed a deregulated mitochondrial system, abnormal amyloidogenic pathway activation, and cognitive functions which were significantly regulated by melatonin treatment in the mice. These findings provide evidence, for the first time, that rmTBI induces brain energy imbalance and reduces neuronal cell survival, and that melatonin treatment overcomes energy depletion and protects against brain damage via the regulation of p-AMPK/p-CREB signaling pathways in the mouse brain.