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Human serum albumin (HSA) is an important carrier protein in plasma with various functions, and it is exposed to glycation. Alkaloids are diverse compounds that have showed different anti-glycation activities. The present study aimed to investigate the anti-glycation activity of thirty alkaloid compounds. First, the compounds were studied via Lipinski's rule; then, among thirty alkaloids, twenty-three were further designated for docking study, using AutoDock program. Three compounds which provided the minimum docking score were selected for further assays. Jatrorrhizine displayed potential activity to inhibit the HSA glycation. The stability of the jatrorrhizine-HSA complex was confirmed by molecular dynamics simulation (MDs). To approve the efficacy of this compound, future in vitro and in vivo studies are required. [ABSTRACT FROM AUTHOR]

SARS-CoV-2 is a corona virus that has been the cause for one of the deadliest pandemics of history, started since 2019. Suppressing the activity of the critical enzymes in the SARS-CoV-2 could potentially inhibit a vital step in viral life cycle. Papain-like protease (PLpro) could be regarded as a critical enzyme in viral replication of SARS-CoV-2. In this research, it was aimed to suppress the activity of PLpro enzyme by using potential plant-derived protease inhibitor peptides. For this purpose, 11 plant derived peptides that could potentially inhibit protease activity were selected from literature. The structures of the PLpro and the peptide ligands were acquired from PDB (protein data bank) and after structural optimization, were docked by using HADDOCK 2.4 program. Analyzing the results indicated that VcTI from Veronica hederifolia provides effective molecular interactions at both liable Zn site and classic active site of PLpro, making it a potential inhibitory ligand for this enzyme that could be used for halting the replication of SARS-CoV-2. Molecular dynamic assay confirmed that the selected receptor and ligand complex was stable. Future in vitro and in vivo investigations are required to verify the efficiency of this compound as a potential therapeutic against SARS-CoV-2 infection. [ABSTRACT FROM AUTHOR]

Inflammation is a natural protective response toward various simulators, including tissue damage or pathogens. The cyclooxygenase-2 (COX-2) is a very important protein in triggering pain and inflammation. Previous studies have claimed that Allium sativum offers a wide range of anti-inflammatory therapeutics for human consumption. Drug discovery is a complicated process, though in silico methods can make this procedure simpler and more cost-effective. At the current study, we performed the virtual screening of eight Allium sativum–derived compounds via molecular docking with COX-2 enzyme and confirmed the binding energy by docking score estimate followed by ADMET and drug-likeness investigation. The resulting highest-docking scored compound was exposed to molecular dynamics simulation (MDS) for evaluating stability of the docked enzyme-ligand complex and to gauge the oscillation and conformational alterations for the time of enzyme-ligand interaction. The factors of RMSD, RMSF, hydrogen bond interactions, and Rg after 100 ns of MDS proved the stability of alliin in the active site of COX-2 in comparison with celecoxib (CEL) as the control. Moreover, we investigated the binding affinity analysis of all compounds via MM/PBSA method. The results from this study suggest that alliin (a sulfuric compound) exhibits a higher binding affinity for the COX-2 enzyme compared to the other compounds and CEL. Alliin showed to be a possible anti-inflammatory therapeutic candidate for managing the inflammatory conditions. [ABSTRACT FROM AUTHOR]

Designing an effective vaccine against different subtypes of Influenza A virus is a critical issue in the field of medical biotechnology. At the current study, a novel potential multi-epitope vaccine candidate based on the neuraminidase proteins for seven subtypes of Influenza virus was designed, using the in silico approach. Potential linear B-cell and T-cell binding epitopes from each neuraminidase protein (N1, N2, N3, N4, N6, N7, N8) were predicted by in silico tools of epitope prediction. The selected epitopes were joined by three different linkers, and physicochemical properties, toxicity, and allergenecity were investigated. The final multi-epitope construct was modeled using GalaxyWEB server, and the molecular interactions with immune receptors were investigated and the immune response simulation assay was performed. A multi-epitope construct with GPGPGPG linker with the lowest allergenicity and highest stability was selected. The molecular docking assay indicated the interactions with immune system receptors, including HLA1, HLA2, and TLR-3. Immune response simulation detected both humoral and cellular response, including the elevated count of B-cells, T-cell, and Nk-cells. [ABSTRACT FROM AUTHOR]

Diabetes mellitus is a metabolic syndrome characterized by elevated blood glucose. The α-glucosidase enzyme is responsible for the hydrolysis of carbohydrates. This in silico study aimed to evaluate the inhibitory effects of the isolated compounds from Allium sativum L. on α-glucosidase. At first, sulfur and phenolic compounds of A. sativum L. were obtained from PubChem database, and α-glucosidase enzyme structure was obtained from Protein Data Bank. Toxicity class of compounds and the Lipinski parameter were predicted by Toxtree and Protox II and the Swiss ADME tools, respectively. Finally, the molecular interaction analysis between α-glucosidase and compounds from A. sativum L. was performed by AutoDock 4.2.6. Molecular interactions were investigated using Discovery Studio Visulizer and Ligplot 2.1 program. All of the selected sulfur and phenolic compounds from A. sativum L. followed the Lipinski's rules, had an acceptable binding energy, and lacked toxicity; therefore, they were appropriate candidates for α-glucosidase inhibition. Among these compounds, methionol and caffeic acid showed the lowest binding energy, and the highest inhibitory effect on α-glucosidase enzyme with − 3.9 and − 4.8 kcal/mol, respectively. These compounds also indicated the lower binding energy than the standard inhibitor (miglitol). Among the sulfur and phenolic compounds in A. sativum L., methionol and caffeic acid were predicted to be the powerful inhibitors, due to having more hydrogen binds and hydrophobic interactions with the active site of α-glucosidase. [ABSTRACT FROM AUTHOR]