Inhibition of the predicted allosteric site of the SARS-CoV-2 main protease through flavonoids

Since its emergence in 2019, coronavirus infection (COVID-19) has become a global pandemic and killed several million people worldwide. Even though several types of vaccines are available against the COVID-19 virus, SARS-CoV-2, new strains are emerging that pose a constant danger to vaccine effectiveness. In this computational study, we identified and predicted potent allosteric inhibitors of the SARS-CoV-2 main protease (Mpro). Via molecular docking and simulations, more than 100 distinct flavonoids were docked with the allosteric site of Mpro. Docking experiments revealed four top hit compounds (Hesperidin, Schaftoside, Brickellin, and Marein) that bound strongly to the Mpro predicted allosteric site. Simulation analyses further revealed that these continually interacted with the enzyme’s allosteric region throughout the simulation time. ADMET and Lipinski drug likenesses were calculated to indicate the therapeutic value of the top four hits: They were non-toxic and exhibited high human intestinal absorption concentrations. These novel allosteric site inhibitors provide a higher chance of drugging SARS-CoV2 Mpro due to the rapid mutation rate of the viral enzyme’s active sites. Our findings provide a new avenue for developing novel allosteric inhibitors of SARS-CoV-2 Mpro. Communicated by Ramaswamy H. Sarma</p

Image_1_Postharvest physiology and biochemistry of Valencia orange after coatings with chitosan nanoparticles as edible for green mold protection under room storage conditions.jpeg

Because of their unique features, nanomaterials have been proposed and have gained acceptance in postharvest applications in fruit. Increasing the storage life and improving the quality of Valencia oranges was investigated using nano-chitosan. A chitosan nanoparticle was prepared by using high-energy ball milling. Chitosan nanoparticles were characterized by Dynamic light scattering, FTIR spectroscopy and Surface morphology by transmission electron microscopy. Fully mature Valencia oranges were harvested and then coated with one of these concentrations (0.2, 0.4, and 0.8% nano-chitosan) and control. The fruits were stored under room storage conditions for 75 days. The quality parameters (fruit weight losses, fruit decay percentage, fruit firmness, total acidity, total soluble solids percentage and T.S.S./acid ratio, ascorbic acid content) were taken in biweekly intervals after 0, 15, 30, 45, 60, and 75 days. Beside the in vitro testing of antifungal activity of chitosan nanoparticles. According to the findings of the two succeeding seasons, the nano-chitosan 0.8% treatment showed the best effects and had the lowest rate of fruit weight loss, fruit deterioration, and T.S.S./acid ratio in comparison to the other treatments in both seasons. Furthermore, the 0.8% nano-chitosan reveled the highest levels of fruit hardness and fruit pulp firmness. Fruit weight loss, fruit deterioration, TSS, and TSS/acid ratio, as well as other metrics, were steadily elevated prior to the storage time. The best results were obtained when Valencia oranges fruits were treated with 0.8% nano-chitosan for 75 days at room temperature.</p

Data_Sheet_1_Bee chitosan nanoparticles loaded with apitoxin as a novel approach to eradication of common human bacterial, fungal pathogens and treating cancer.docx

Antimicrobial resistance is one of the largest medical challenges because of the rising frequency of opportunistic human microbial infections across the globe. This study aimed to extract chitosan from the exoskeletons of dead bees and load it with bee venom (commercially available as Apitoxin [Api]). Then, the ionotropic gelation method would be used to form nanoparticles that could be a novel drug-delivery system that might eradicate eight common human pathogens (i.e., two fungal and six bacteria strains). It might also be used to treat the human colon cancer cell line (Caco2 ATCC ATP-37) and human liver cancer cell line (HepG2ATCC HB-8065) cancer cell lines. The x-ray diffraction (XRD), Fourier transform infrared (FTIR), and dynamic light scattering (DLS) properties, ζ-potentials, and surface appearances of the nanoparticles were evaluated by transmission electron microscopy (TEM). FTIR and XRD validated that the Api was successfully encapsulated in the chitosan nanoparticles (ChB NPs). According to the TEM, the ChB NPs and the ChB NPs loaded with Apitoxin (Api@ChB NPs) had a spherical shape and uniform size distribution, with non-aggregation, for an average size of approximately 182 and 274 ± 3.8 nm, respectively, and their Zeta potential values were 37.8 ± 1.2 mV and − 10.9 mV, respectively. The Api@ChB NPs had the greatest inhibitory effect against all tested strains compared with the ChB NPs and Api alone. The minimum inhibitory concentrations (MICs) of the Api, ChB NPs, and Api@ChB NPs were evaluated against the offer mentioned colony forming units (CFU/mL), and their lowest MIC values were 30, 25, and 12.5 μg mL−1, respectively, against Enterococcus faecalis. Identifiable morphological features of apoptosis were observed by 3 T3 Phototox software after Api@ChB NPs had been used to treat the normal Vero ATCC CCL-81, Caco2 ATCC ATP-37, and HepG2 ATCC HB-8065 cancer cell lines for 24 h. The morphological changes were clear in a concentration-dependent manner, and the ability of the cells was 250 to 500 μg mL−1. These results revealed that Api@ChB NPs may be a promising natural nanotreatment for common human pathogens.</p