Polyphenolic Compounds Isolated from Marine Algae Attenuate the Replication of SARS-CoV-2 in the Host Cell through a Multi-Target Approach of 3CLpro and PLpro

A global health concern has emerged as a response to the recent SARS-CoV-2 pandemic. The identification and inhibition of drug targets of SARS-CoV-2 is a decisive obligation of scientists. In addition to the cell entry mechanism, SARS-CoV-2 expresses a complicated replication mechanism that provides excellent drug targets. Papain-like protease (PL^pro) and 3-chymotrypsin-like protease (3CL^pro) play a vital role in polyprotein processing, producing functional non-structural proteins essential for viral replication and survival in the host cell. Moreover, PL^pro is employed by SARS-CoV-2 for reversing host immune responses. Therefore, if some particular compound has the potential to interfere with the proteolytic activities of 3CL^pro and PL^pro of SARS-CoV-2, it may be effective as a treatment or prophylaxis for COVID-19, reducing viral load, and reinstating innate immune responses. Thus, the present study aims to inhibit SARS-CoV-2 through 3CL^pro and PL^pro using marine natural products isolated from marine algae that contain numerous beneficial biological activities. Molecular docking analysis was utilized in the present study for the initial screening of selected natural products depending on their 3CL^pro and PL^pro structures. Based on this approach, Ishophloroglucin A (IPA), Dieckol, Eckmaxol, and Diphlorethohydroxycarmalol (DPHC) were isolated and used to perform in vitro evaluations. IPA presented remarkable inhibitory activity against interesting drug targets. Moreover, Dieckol, Eckmaxol, and DPHC also expressed significant potential as inhibitors. Finally, the results of the present study confirm the potential of IPA, Dieckol, Eckmaxol, and DPHC as inhibitors of SARS-CoV-2. To the best of our knowledge, this is the first study that assesses the use of marine natural products as a multifactorial approach against 3CL^pro and PL^pro of SARS-CoV-2.     

Challenges in wide implementation of genome editing for crop improvement

Genome editing technologies using customizable sequence specific nucleases (SSNs) enables precise genome modification in plants, which has revolutionized functional genomics research as well as crop improvement. Applicability of SSN-mediated genome editing ranges from targeted gene knockout and single base modification to multiple gene stacking into desired genomic sites. However, there are still considerable challenges in implementing genome editing technologies for practical crop improvement. Here, we briefly discuss the technological challenges, especially those associated with the delivery of SSNs and with homologous recombination-mediated genome editing, and address some promising solutions to overcome the issues.     

Cytoprotective Peptides from Blue Mussel Protein Hydrolysates: Identification and Mechanism Investigation in Human Umbilical Vein Endothelial Cells Injury

Cardiovascular disease represents a leading cause of mortality and is often characterized by the emergence of endothelial dysfunction (ED), a physiologic condition that takes place in the early progress of atherosclerosis. In this study, two cytoprotective peptides derived from blue mussel chymotrypsin hydrolysates with the sequence of EPTF and FTVN were purified and identified. Molecular mechanisms underlying the cytoprotective effects against oxidative stress which lead to human umbilical vein endothelial cells (HUVEC) injury were investigated. The results showed that pretreatment of EPTF, FTVN and their combination (1:1) in 0.1 mg/mL significantly reduced HUVEC death due to H₂O₂ exposure. The cytoprotective mechanism of these peptides involves an improvement in the cellular antioxidant defense system, as indicated by the suppression of the intracellular ROS generation through upregulation of the cytoprotective enzyme heme oxygenase-1. In addition, H₂O₂ exposure triggers HUVEC damage through the apoptosis process, as evidenced by increased cytochrome C release, Bax protein expression, and the elevated amount of activated caspase-3, however in HUVEC pretreated with peptides and their combination, the presence of those apoptotic stimuli was significantly decreased. Each peptide showed similar cytoprotective effect but no synergistic effect. Taken together, these peptides may be especially important in protecting against oxidative stress-mediated ED.     

Coronaviruses in cattle

Bovine coronaviruses are spread all over the world. They cause two types of clinical manifestations in cattle either an enteric, calf diarrhoea and winter dysentery in adult cattle, or respiratory in all age groups of cattle. The role of coronaviruses in respiratory infections is still a hot topic of discussion since they have been isolated from sick as well as healthy animals and replication of disease is rarely successful. Bovine coronavirus infection is characterised by high morbidity but low mortality. The laboratory diagnosis is typically based on serological or molecular methods. There is no registered drug for the treatment of virus infections in cattle and we are limited to supportive therapy and preventative measures. The prevention of infection is based on vaccination, biosecurity, management and hygiene. This paper will cover epidemiology, taxonomy, pathogenesis, clinical signs, diagnosis, therapy, economic impact and prevention of coronavirus infections in cattle.

     

Lipid Inhibitory Effect of (−)-loliolide Isolated from Sargassum horneri in 3T3-L1 Adipocytes: Inhibitory Mechanism of Adipose-Specific Proteins

Sargassum horneri (S. horneri) is a well-known brown seaweed widely distributed worldwide. Several biological activities of S. horneri have been reported. However, its effects on lipid metabolism and the underlying mechanisms remain elusive. In the present study, we examined the inhibitory effect of the active compound “(−)-loliolide ((6S,7aR)-6-hydroxy-4,4,7a-trimethyl-5,6,7,7a-tetrahydro-1-benzofuran-2(4H)-one (HTT))” from S. horneri extract on lipid accumulation in differentiated adipocytes. MTT assays demonstrated that (−)-loliolide is not toxic to 3T3-L1 adipocytes in a range of concentrations. (−)-loliolide significantly reduced intracellular lipid accumulation in the differentiated phase of 3T3-L1 adipocytes as shown by Oil Red O staining. Western blot analysis revealed that (−)-loliolide increased the expression of lipolytic protein phospho-hormone-sensitive lipase (p-HSL) and thermogenic protein peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1). Additionally, (−)-loliolide decreased expression of adipogenic and lipogenic proteins, including sterol regulatory element-binding protein-1 (SREBP-1), peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer-binding protein-α (C/EBP-α), and fatty acid-binding protein 4 (FABP4) in 3T3-L1 adipocytes. These results indicate that (−)-loliolide from S. horneri could suppress lipid accumulation via regulation of antiadipogenic and prolipolytic mechanisms in 3T3-L1 cells. Considering the multifunctional effect of (−)-loliolide, it can be useful as a lipid-lowering agent in the management of patients who suffer from obesity.     

Effects of Ethanol Extracts from Grateloupia elliptica,a Red Seaweed,and Its Chlorophyll Derivative on 3T3-L1 Adipocytes: Suppression of Lipid Accumulation through Downregulation of Adipogenic Protein Expression

Grateloupia elliptica (G. elliptica) is a red seaweed with antioxidant, antidiabetic, anticancer, anti-inflammatory, and anticoagulant activities. However, the anti-obesity activity of G. elliptica has not been fully investigated. Therefore, the effect of G. elliptica ethanol extract on the suppression of intracellular lipid accumulation in 3T3-L1 cells by Oil Red O staining (ORO) was evaluated. Among the eight red seaweeds tested, G. elliptica 60% ethanol extract (GEE) exhibited the highest inhibition of lipid accumulation. GEE was the only extract to successfully suppress lipid accumulation among ethanol extracts from eight red seaweeds. In this study, we successfully isolated chlorophyll derivative (CD) from the ethyl acetate fraction (EA) of GEE by high-performance liquid chromatography and evaluated their inhibitory effect on intracellular lipid accumulation in 3T3-L1 adipocytes. CD significantly suppressed intracellular lipid accumulation. In addition, CD suppressed adipogenic protein expression such as sterol regulatory element-binding protein-1 (SREBP-1), peroxisome proliferator-activated receptor-γ (PPAR-γ), CCAAT/enhancer-binding protein-α (C/EBP-α), and fatty acid binding protein 4 (FABP4). Taken together, our results indicate that CD from GEE inhibits lipid accumulation by suppressing adipogenesis via the downregulation of adipogenic protein expressions in the differentiated adipocytes. Therefore, chlorophyll from G. elliptica has a beneficial effect on lipid metabolism and it could be utilized as a potential therapeutic agent for preventing obesity.     

Reduction of adult hippocampal neurogenesis is amplified by aluminum exposure in a model of type 2 diabetes

In this study, we investigated the effects of chronic aluminum (Al) exposure for 10 weeks on cell proliferation and neuroblast differentiation in the hippocampus of type 2 diabetic rats. Six-week-old Zucker diabetic fatty (ZDF) and Zucker lean control (ZLC) rats were selected and randomly divided into Al- and non-Al-groups. Al was administered via drinking water for 10 weeks, after which the animals were sacrificed at 16 weeks of age. ZDF rats in both Al- and non-Al-groups showed increases in body weight and blood glucose levels compared to ZLC rats. Al exposure did not significantly affect body weight, blood glucose levels or pancreatic β-cells and morphology of the pancreas in either ZLC or ZDF rats. However, exposure to Al reduced cell proliferation and neuroblast differentiation in both ZLC and ZDF rats. Exposure to Al resulted in poor development of the dendritic processes of neuroblasts in both ZLC and ZDF rats. Furthermore, onset and continuation of diabetes reduced cell proliferation and neuroblast differentiation, and Al exposure amplified reduction of these parameters. These results suggest that Al exposure via drinking water aggravates the impairment in hippocampal neurogenesis that is typically observed in type 2 diabetic animals.