Background: 2019-nCoVis, a novel coronavirus was isolated and identified in 2019 in the city of Wuhan, China. On February 17, 2020 and according to the World Health Organization, 71, 429 confirmed cases worldwide were identified, among them 2162 new cases were recorded in the last 24 hours. One month later, the confirmed cases jumped to 179111, with 11525 new cases in the last 24 hours, with 7426 total deaths. No drug or vaccine is present at the moment for human and animal coronavirus. Methods: The inhibition of 3CL hydrolase enzyme provides a promising therapeutic principle for developing treatments against CoViD-19. The 3CLpro (Mpro) is known for involving in counteracting the host innate immune response. Results: This work presents the inhibitory effect of some natural compounds against 3CL hydrolase enzyme, and explains the main interactions in inhibitor-enzyme complex. Molecular docking study was carried out using Autodock Vina. By screening several molecules, we identified three candidate agents that inhibit the main protease of coronavirus. Hispidin, lepidine E, and folic acid are bound tightly in the enzyme, therefore strong hydrogen bonds have been formed (1.69-1.80Å) with the active site residues. Conclusion: This study provides a possible therapeutic strategy for CoViD-19.

Fenugreek (Trigonella foenum-graecum) has a great beneficial health effect; it has been used in traditional medicine by many cultures. Likewise, the α-amylase inhibitors are potential compounds in the development of drugs for the treatment of diabetes. The beneficial health effects of fenugreek lead us to explore the chemical composition of the seeds and their antioxidant and α-amylase inhibition activities. The flavonoid extraction from fenugreek seeds was achieved with methanol through a Soxhlet apparatus. Then, the flavonoid glycosides were characterized using HPLC-DAD-ESI-MS analysis. The antioxidant capacity of fenugreek seed was measured using DPPH, FRAP, ABTS, and CUPRAC assays. Finally, the α-amylase inhibition activity was carried out using in vitro and in silico methods. The methanolic extract was found to contain high amounts of total phenolics (154.68 ± 1.50 μg GAE/mg E), flavonoids (37.69 ± 0.73 μg QE/mg E). The highest radical-scavenging ability was recorded for the methanolic extract against DPPH (IC₅₀ = 556.6 ± 9.87 μg/mL), ABTS (IC₅₀ = 593.62 ± 9.35 μg/mL). The ME had the best reducing power according to the CUPRAC (A 0.5 = 451.90 ± 9.07 μg/mL). The results indicate that the methanolic extracts of fenugreek seed best α-amylase inhibition activities IC₅₀ = 653.52 ± 3.24 μg/mL. Twenty-seven flavonoids were detected, and all studied flavonoids selected have good affinity and stabilize very well in the pocket of α-amylase. The interactions between the studied flavonoids with α-amylase were investigated. The flavonoids from fenugreek seed present a good inhibitory effect against α-amylase, which is beneficial for the prevention of diabetes and its complications.

The black fungus is a SARS-CoV-2-associated fungal co-infection. Mechanisms by which antifungal drugs act against Mucormycosis are by inhibition of enzymes implicated in ergosterol biosynthesis or cell wall formation or the drug interaction directly with ergosterol. Since it has been shown that the reduction of ergosterol biosynthesis prevents this infection, we carried out a virtual screening with molecular docking analysis and tested a dataset of 880 molecules for its effects on an enzyme involved in ergosterol biosynthesis (CYP51) and fungal infection (lipase), as well as ADMET and toxicity properties of the studied molecules. We calculated the stability of the complex’s inhibitor-enzyme throughout the time using molecular dynamics simulations. From this, initial screening indicated that 600 out of a total of 880 compounds have a good affinity towards sterol 14α-demethylase. The two compounds ZINC95486139 and ZINC33833639 were determined as safe and have good drug-likeness properties, and have binding energies of −75.07 and −83.89 kcal/mol, respectively by MMGBSA and create strong and stable interactions with the residues of the active site of the enzyme. To the best of our knowledge, ZINC95486139 and ZINC33833639 have not yet been described in the literature as anti-sterol 14α-demethylase inhibitors or evaluated for their anti-fungal activity.

Excessive intake of purine-rich foods such as seafood and red meat leads to excess xanthine oxidase activity and provokes gout attacks. The aim of this paper is to evaluate in vitro and in silico, the inhibition effect of Cupressus sempervirens plant extracts (flavonoids (Cae) and alkaloids (CaK)) and its six derivative compounds on bovine xanthine oxidase (BXO). The in silico study consists of molecular docking with GOLD v4.0 based on the best PLPchem score (PLP) and prediction of biological activity with the PASS server tool. The inhibitors used were lignan (cp1), Amentoflavone (cp2), Cupressuflavone (cp3), Isocryptomerin (cp4), Hinokiflavone (cp5), and Neolignan (cp6). The in vitro results showed that CaK gives an IC50 of 3.52 ± 0.04 μg/ml. Similarly, Cae saved an IC50 of 8.46 ± 1.98 μg/ml compared with the control (2.82 ± 0.10 μg/ml). The in silico results show that cp1 was the best inhibitor model (PLP of 88.09) with approved pharmacokinetics. These findings suggest that cp1 and cp2 may offer good alternatives for the treatment of hyperuricemia; cp3 was moderate, while the others (cp4 to cp6) were considered weak inhibitors according to their PLP. Communicated by Ramaswamy H. Sarma

Background and Objective: Lipase inhibitors have aroused a great interest because they could help in the therapy of many diseases but, unfortunately, only a few drugs are currently available on the market. Therefore, the aim of this work was to evaluate for the first time the lipase inhibition effect of Thapsia garganica extracts from seeds, leaves and roots. Methods: Polyphenols and flavonoids contents were determined using spectrophotometric method. Inhibitory activity of ethyl acetate extracts from seeds, leaves and roots of T. garganica against Candida rugosa lipase were determined. To uncover the active constituents responsible for this anti-lipase activity, further investigations were performed by employing theoretical docking simulations, using AutoDock Vina program to discuss the nature of interactions and the inhibition mechanism by major bioactive compounds synthesized by this plant. Results: Seeds, leaves and roots extracts of T. garganica showed appreciable contents of polyphenols and flavonoids which is most in seeds extract with 2.90±0.02 mg GAE/gdw and 1.53±0.05 mg QE/gdw, respectively. Hence, their inhibitory activities against Candida rugosa lipase were determined as IC50 of 1.19 mg / ml, 1.96 mg /ml and 1.87 mg/ml, respectively. Docking simulations shown that nortribolid and tribolid are best inhibitors for both lipases (Candida rugosa and human pancreatic lipases). Conclusion: Testing the anti-lipase activity of the ethyl acetate extracts of T. garganica revealed a potent lipase inhibition activity, which suggest the use of these molecules as anti-obesity drugs.

Objective: The present study is carried out to screen the anticholinesterase effect of the total alkaloids of L. sativum seeds and other plants, and studied the ability of Lepidine B to inhibit AChE, BuChE, BACE and MAGL. and the main interactions in inhibitor-enzyme complex. Method: Inhibitory effect extracts from Lepidium sativum, Juniperus phoenicea and Juniperus oxycedrus on acetylcholinesterase using Ellman method have been investigated using Donepezil as positive control. Molecular docking study carried out using Autodock vina. The structures of studied molecules Lepidine B, Galantamine and Donepezil were obtained from PubChem database and Protein databank. Results: Alkaloidal extract of Lepidium sativum and ethyl acetate extracts of Juniperus phoenicea and Juniperus oxycedrus exhibit a strong acetylcholinesterase inhibitory activity with IC50 values of 0.59 ± 0.04, 0.57 ± 0.00 and 0.49 ± 0.00 mg/mL, respectively using Donepezil <0.25 mg/mL as positive control. The major component of alkaloid of L. sativum, Lepidine B bind so tightly to AChE and BuChE as much as galantamine and donepezil. We suggest that Lepidine B is a non-competitive inhibitory by interacting with PAS of AChE and BuChE, therefore it is capable to prevent the HuAChE-induced Aβ aggregation. We have found significant interactions in the Lepidine B-BACE and Lepidine B-MAGL complexes. Conclusion: The docking study indicate that Lepidine B is a promising anti-AD drug and might become a drug candidate to prevent Alzheimer's disease due to its multiple roles as potent inhibitor for AChE, BuChE, BACE and MAGL, also inhibitor for Aβ fibrillogenesis. No previous results about the inhibitory effect Lepidine B on the AChE, BuChE, β secretase and monoacylglycerol lipase have been reported.