Showing papers in "International Journal of Peptide Research and Therapeutics in 2021"
TL;DR: This review enlightens the various peptide sources and the different approaches that have contributed to the search of potential antiviral peptides and illustrates the applications of few advanced techniques to measure the binding parameters such as affinity and kinetics of the screened interacting partners.
Abstract: Despite rapid advances in the human healthcare, the infection caused by certain viruses results in high morbidity and mortality accentuate the importance for development of new antivirals. The existing antiviral drugs are limited, due to their inadequate response, increased rate of resistance and several adverse side effects. Therefore, one of the newly emerging field "peptide-based therapeutics" against viruses is being explored and seems promising. Over the last few years, a lot of scientific effort has been made for the identification of novel and potential peptide-based therapeutics using various advanced technologies. Consequently, there are more than 60 approved peptide drugs available for sale in the market of United States, Europe, Japan, and some Asian countries. Moreover, the number of peptide drugs undergoing the clinical trials is rising gradually year by year. The peptide-based antiviral therapeutics have been approved for the Human immunodeficiency virus (HIV), Influenza virus and Hepatitis virus (B and C). This review enlightens the various peptide sources and the different approaches that have contributed to the search of potential antiviral peptides. These include computational approaches, natural and biological sources (library based high throughput screening) for the identification of lead peptide molecules against their target. Further the applications of few advanced techniques based on combinatorial chemistry and molecular biology have been illustrated to measure the binding parameters such as affinity and kinetics of the screened interacting partners. The employment of these advanced techniques can contribute to investigate antiviral peptide therapeutics for emerging infections.
70 citations
TL;DR: In this review information about antimicrobial activity, various properties, mechanism and sources of AMPs along with how these properties are exploited for the application of efficient and promising drug agents in pharmaceutical companies has been discussed.
Abstract: The growth of pathogens across the globe is developing at a very fast rate, thus turning into a worldwide health problem. Since, current treatment alternatives have failed to a large extent, novel antibiotics are highly in demand. Antimicrobial peptides (AMPs) have become a significant alternative in this scenario because of their wide-spectrum activity, rapid killing and often cell selectivity. They comprise diverse functional molecules with multifaceted properties, consisting of varied biological activity. Because of the different amino acids and elements in its structure, their action mechanism is specifically altered. Most of the AMPs have been derived from animals, plants and marine sources. They show therapeutic potential, yet, their use is limited because of their short plasma half-life. AMP production can be done at reasonable costs with the help of biotechnological methods. Thus, discovery of an efficient and long-lasting antimicrobial drugs is awaited as soon as these challenges are overcome. The market of antimicrobial peptides is growing at a fast rate. Bioactive peptides from natural sources open up new opportunities to discover lead molecules for management of various ailments. This systematic review centres around the antimicrobial activity, various properties, mechanism and sources of AMPs along with how these properties are exploited for the application of efficient and promising drug agents in pharmaceutical companies. Therefore, in this review information about antimicrobial activity, various properties, mechanism and sources of AMPs along with how these properties are exploited for the application of efficient and promising drug agents in pharmaceutical companies has been discussed.
42 citations
TL;DR: This article is an augmentation to technical literatures on the cancer subject and an academic exposure of the food-originated approach for its management.
Abstract: Cancer has gained appreciable attention in the category of noncommunicable health disorders as the group of proliferative diseases and metabolic syndromes of fatal consequence, globally. The conventional chemotherapeutic, radiological and associated pharmacotherapeutic advances for its cure have timelessly displayed severe aftereffects in patients. Furthermore, the underlying costs and technical requirements of these have added to their limitation recitals. Food-derived bioactive peptides have been scientifically proven as suitable alternatives for cancer management. Studies have shown that some attributes they possess such as specificity, smaller sizes, better ease of syntheses and modification, and improved penetration into cell membranes make them better alternatives to some protein isolates. Their comparative precedencies with regards to natural and efficacy with minimal side effects have offered them the recognition as proficient options in cancer therapy. This review integrates contemporary technical information about bioactive peptides from plants and animal foods and food by-products and their experimentally determined potentials as remedies for cancer. Furthermore, technical details about their isolation methodologies are offered. This article is an augmentation to technical literatures on the cancer subject and an academic exposure of the food-originated approach for its management.
36 citations
TL;DR: A broad spectrum of knowledge is explained on piscidin, its classes and types, structure, cytotoxicity, membrane permeabilization, properties and therapeutical implications.
Abstract: Antimicrobial peptides (AMPs) are short molecules produced by almost all organisms. Fish AMPs contain innate immune components as their primary immune molecules. The fish AMPs include piscidins, hepcidins, defensins, cathelicidins and histone-derived peptides. Piscidin is potent and broad-spectrum; this peptide was conserved among Acanthopterygii superorder and is therapeutically important among other AMPs. It was present mainly in the tissues of gills, muscle, head-kidney, skin and intestine of teleost. Piscidin AMP family includes piscidin, moronecidin, pleurocidin, epinecidin, gaduscidin, misgurin, dicentracin, chrysophsin and myxinidin. This review reports the structural properties of various piscidin and their mode of action as it is important to know their mechanism how the peptide involved in antimicrobial activity. In addition, the gene expression of piscidin which influenced the immune responses, their pharmaceutical importance and biological applications were described. Overall, the review explains a broad spectrum of knowledge on piscidin, its classes and types, structure, cytotoxicity, membrane permeabilization, properties and therapeutical implications.
31 citations
TL;DR: Fish protein hydrolysates possess numerous bioactivity potentials such as antioxidant, antimicrobial, anti-tumor, ACE inhibiting activity, calcium binding properties, and anticoagulant properties, but information on transportation and bioavailability of FPHs in gastro-intestinal system is limited.
Abstract: Fish protein hydrolysates (FPHs) are rich source of amino acids and peptides that are beneficial to human health. Industrially, when fish are processed, huge amount of wastes are generated. These wastes are often discarded into waterways, seas, oceans or even buried in the ground. However, these wastes can be processed into FPHs using enzymatic hydrolysis. Generally, FPHs possess numerous bioactivity potentials such as antioxidant, antimicrobial, anti-tumor, ACE inhibiting activity, calcium binding properties, and anticoagulant properties. All of which were reviewed and presented in this article. In addition, their application in food, agriculture and pharmaceutical industries were explored. Nevertheless, despite the numerous bioactivities of FPHs, information on transportation and bioavailability of FPHs in gastro-intestinal system is limited. Thus, it was suggested that further work should be carried out in this aspect to validate their action, mechanism and therapeutic value in the gastro-intestinal system. This will enhance their potentials as a nutritive ingredient in the emerging nutraceutical and pharmaceutical commercial markets.
24 citations
TL;DR: Bioprocess conditions namely temperature, pH, agitation and duration were comparatively modeled using statistical and artificial neural network methods to predict and optimize product yield using the matrix of a central composite rotatable design (CCRD).
Abstract: A freshwater alkaliphilic strain of Pseudomonas aeruginosa, grown on waste frying oil-basal medium, produced a surface-active metabolite identified as glycolipopeptide. Bioprocess conditions namely temperature, pH, agitation and duration were comparatively modeled using statistical and artificial neural network (ANN) methods to predict and optimize product yield using the matrix of a central composite rotatable design (CCRD). Response surface methodology (RSM) was the statistical approach while a feed-forward neural network, trained with Levenberg–Marquardt back-propagation algorithm, was the neural network method. Glycolipopeptide model was predicted by a significant (P < 0.001, R2 of 0.9923) quadratic function of the RSM with a mean squared error (MSE) of 3.6661. The neural network model, on the other hand, returned an R2 value of 0.9964 with an MSE of 1.7844. From all error metrics considered, ANN glycolipopeptide model significantly (P < 0.01) outperformed RSM counterpart in predictive modeling capability. Optimization of factor levels for maximum glycolipopeptide concentration produced bioprocess conditions of 32 °C for temperature, 7.6 for pH, agitation speed of 130 rpm and a fermentation time of 66 h, at a combined desirability function of 0.872. The glycosylated lipid-tailed peptide demonstrated significant anti-bacterial activity (MIC = 8.125 µg/mL) against Proteus vulgaris, dose-dependent anti-biofilm activities against Escherichia coli (83%) and Candida dubliniensis (90%) in 24 h and an equally dose-dependent cytotoxic activity against human breast (MCF-7: IC50 = 65.12 µg/mL) and cervical (HeLa: IC50 = 16.44 µg/mL) cancer cell lines. The glycolipopeptide compound is recommended for further studies and trials for application in human cancer therapy.
23 citations
TL;DR: Wang et al. as discussed by the authors developed a novel vaccine construct using B-cell derived T-cell epitopes from four target antigenic proteins (HpaA, FlaA and Omp18), and found the induction of possible immune response using advanced immunoinformatics approaches.
Abstract: Helicobacter pylori is a highly potential pathogen to colonize in the human stomach. This bacterial strain is now alarming serious health concern all over the world. Combating through available drugs is a difficult task due to lack of appropriate common targets against genetically diverse strains. Therefore, the developments of effective targets vaccines require alternative strategies to eliminate the H. pylori infection. In this study, we developed a novel vaccine construct using B-cell derived T-cell epitopes from four target antigenic proteins (HpaA, FlaA, FlaB and Omp18), and found the induction of possible immune response using advanced immunoinformatics approaches. In order to boost immune system, we tagged adjuvant (50S ribosomal protein L7/L12) with a suitable linker at the N-terminus side of vaccine sequence. Protein–protein docking between human Toll like receptor 5 (TLR5) and vaccine construct help to predict the way of inductive signaling that leads to immune-response. The calculated negative score (− 151.4, + / − 8.7) of molecular docking complex signify the best binding interface. Molecular dynamics simulation studies confirmed the proper docking between TLR5 and vaccine candidate. Moreover, Normal mode analysis (NMA) calculates the molecular motion of the docking complex. The low eigenvalue (2.935e−05) indicates the stable and flexible molecular motion in the binding interaction side. Finally, in-silico cloning of vaccine candidate was performed using expression vector pET28b (+) with the optimized restriction sites.
23 citations
TL;DR: In this article, a novel antioxidant peptide (NF2-4-1) was identified to be Leu-Thr-Glu-IIeIIe-Pro with 685.41 Da molecular weight utilized matrix-assisted laser desorption/ionization-time of flight mass spectrometry.
Abstract: Chickpea (Cicer arietinum L.) is the second most widely cultivated leguminous plant in the world. In this study, the chickpea sprout protein (CSP) was hydrolyzed by various enzymes (trypsin, neutrase, alcalase and papain). The neutrase fraction (NF) which exhibits the best antioxidant activity with a high degree of hydrolysis (DH) was purified by ion-exchange chromatography (IEC), gel filtration chromatography (GFC), and reverse phase high-performance liquid chromatography (RP-HPLC). A novel antioxidant peptide (NF2-4-1) was identified to be Leu-Thr-Glu-IIe-IIe-Pro with 685.41 Da molecular weight utilized matrix-assisted laser desorption/ionization-time of flight mass spectrometry. The IC50 values of NF2-4-1 was 0.24 ± 0.06 mg/mL on 1, 1-diphenyl-2-picrylhydrazyl (DPPH˙) and 0.57 ± 0.04 mg/mL on hydroxyl radicals (·OH) scavenging activity, respectively. Therefore, the results of this study demonstrate that chickpea sprouts can be used as a source of natural antioxidant peptides for food and nutraceutical applications.
23 citations
TL;DR: The properties of biologically-produced biosurfactants and their antitumor activities against distinctive cancer models are discussed and their potential mechanisms are underlined and light is shed on the discovery of new active bioproducts.
Abstract: Biosurfactants are natural compounds produced biologically by certain bacterial strains. They are promising alternatives in several applications due to their biocompatibility, biodegradability and reduced toxicity. Systemic toxicity problems and drug resistance in tumor chemotherapy are urging the continued discovery of new antitumor agents. Biosurfactants have significant effect in inhibiting multiple tumor types. Specifically, surfactin, iturin, and fengycin lipopeptide biosurfactant were previously produced from several bacterial species belonging to Bacillus genus. Only few previous studies investigated their cytotoxicity against some tumor types such as breast, colon, leukemia, hepatoma and others. Due to the probability of being potential antitumor treatments, biosurfactants nanoparticles could be clinically recommended. This review discussed the properties of biologically-produced biosurfactants and their antitumor activities against distinctive cancer models. Additionally, it underlines their potential mechanisms and sheds light on the discovery of new active bioproducts.
21 citations
TL;DR: The results advocate that the designed vaccine candidate could be an effective and promising weapon to fight with COVID-19 infection worldwide.
Abstract: The COVID-19 disease is caused by SARS-CoV-2 and spreading rapidly worldwide with extremely high infection rate. Since effective and specific vaccine is not available to combat the deadly COVID-19, the objective of our study was to design a multi-epitope vaccine using immunoinformatics approach with translational implications. Nucleocapsid (N) protein of SARS-CoV-2 is stable, conserved and highly immunogenic along with being less prone to mutations during infection, which makes it a suitable candidate for designing vaccine. In our study, B- and T-cells epitopes were identified from N protein and screened based on crucial parameters to design the multi-epitope vaccine construct. Additionally, human beta-defensin-2 was incorporated into the vaccine construct as an adjuvant along with suitable linkers followed by its further evaluation based on crucial parameters including allergenicity, antigenicity, stability etc. Combined major histocompatibility complexes (MHC-I and MHC-II) binding epitopes presented broader population coverage of the vaccine throughout the world. The three-dimensional structure of vaccine candidate implied strong interaction with toll-like receptor 3 (TLR3) using molecular docking. The vaccine-TLR3 complex was observed to be highly stable during simulation and electrostatic free energy was foremost contributor for stabilization of the structure. Subsequently, in silico cloning of vaccine candidate was carried out to generate the construct into pET-28a(+) expression vector succeeded by its virtual confirmation. Altogether, our results advocate that the designed vaccine candidate could be an effective and promising weapon to fight with COVID-19 infection worldwide.
18 citations
TL;DR: The objective of this review is to create a comprehensive resource of anticancer agents from venoms which would foster pharmacogenomic studies and the development of cost-effective cancer treatment.
Abstract: Biologically active compounds with potential anticancer activity have been isolated from various animal sources. Recent research is focused on venoms from animal sources, since they specifically target cancer cells and are less toxic to normal tissues, thus making them a better alternative for prevention and management of cancer. Animals produce pharmacologically active compounds that are capable of protein synthesis inhibition, induction of angiogenesis and apoptosis. Over the past decades, venom has been identified as a potential source of therapeutic agents, including anti-cancer agents. Venoms are isolated from various animal sources such as wasp, honey bee and scorpion are composite mixtures of various peptides, protein, enzymes, toxins and non-proteinaceous secretions. They are natural compounds that act as a template and can be utilized for the development of new therapeutic agents against cancer. The objective of this review is to create a comprehensive resource of anticancer agents from venoms which would foster pharmacogenomic studies and the development of cost-effective cancer treatment. Information about different animal venoms has been compiled after a panoramic literature survey.
TL;DR: The areas on antimicrobial peptides like source, properties, classification, mechanism of action, resistance and strategies for its applications are focused on.
Abstract: Antimicrobial peptides (AMPs) are small sized protein molecules which play a crucial role in host inborn immune framework. AMPs with their specific properties are often considered as a barrier against various harmful foreign particles including bacteria, yeast, fungi and virus. These peptides from different sources exhibit diverse functions and structural features. It exploits the unique property of membrane interaction to destroy target organisms and even cellular components are targeted. However, to combat the emerging resistance towards antibiotics, the use of AMPs as natural drugs has gained importance. Efficiency of these peptides can be enhanced by modification in different aspects through in silico approach. In this article we focus on the areas on antimicrobial peptides like source, properties, classification, mechanism of action, resistance and strategies for its applications.
TL;DR: Four B cell epitopes of K. pneumoniae Fim antigens are found that are immunogen, antigenic, not similar to human peptides, not allergen and not toxic, and suitable physiochemical properties to administrate as vaccine, although their complete efficacy should be also shown in vitro and in vivo.
Abstract: Klebsiella pneumoniae is one of the major causes of nosocomial infections worldwide which can cause several diseases in children and adults. The globally dissemination of hyper-virulent strains of K. pneumoniae and the emergence of antibiotics-resistant isolates of this pathogen narrows down the treatment options and has renewed interest in its vaccines. Vaccine candidates of Klebsiella pneumoniae have not been adequately protective, safe and globally available yet. In K. pneumoniae infection, it is well known that B cells that induce robust humoral immunity are necessary for the host complete protection. Identifying the B cell epitopes of antigens is valuable to design novel vaccine candidates. In the present study using immunoinformatics approaches we found B cell epitopes of four K. pneumoniae type 1 fimbriae antigens namely FimA, FimF, FimG, and FimH. Linear and conformational B cell epitopes of each antigen were predicted using different programs. Subsequently, many bioinformatics assays were applied to choose the best epitopes including prediction antigenicity, toxicity, human similarity and investigation on experimental records. These assays resulted in final four epitopes (each for one Fim protein). These final epitopes were modeled and their physiochemical properties were estimated to be used as potential vaccine candidates. Altogether, we found four B cell epitopes of K. pneumoniae Fim antigens that are immunogen, antigenic, not similar to human peptides, not allergen and not toxic. Also, they have suitable physiochemical properties to administrate as vaccine, although their complete efficacy should be also shown in vitro and in vivo.
TL;DR: An overview of the classification, antimicrobial activities, mode of action, and mechanism of resistance of human AMPs will be provided.
Abstract: Overuse of antibiotics is one of the important factors that contribute to developing antimicrobial resistance. Many studies have been conducted to find out promising solutions to overcome the problems. Antimicrobial peptides (AMPs) are fundamental components of human innate immunity. They have an important role in the treatment of a wide range of diseases, including cancer, allergies, and also in warding off invading pathogens. In the case of infectious disease, the AMPs exhibit broad-spectrum activity against a wide range of pathogens including Gram-positive and -negative bacteria, yeasts, fungi, and enveloped viruses. These peptides have been isolated from various sources such as microorganisms, plants, invertebrates, and vertebrates. The peptides show distinct physicochemical and structural properties but most of them are small cationic peptides with amphipathic properties. In this review, an overview of the classification, antimicrobial activities, mode of action, and mechanism of resistance of human AMPs will be provided. These peptides are categorized into three main groups. The defensins are cationic peptides containing six cysteine residues with three intramolecular disulfide bridges. In humans, two classes of defensins could be found, α-defensins and β-defensins. The second group is cathelicidins that only one AMP, LL-37, has been found in humans. This peptide is derived from proteolytic digestion of the C-terminal of human CAP18 protein. The third group is the family of histatins that are small cationic histidine-rich peptides, and mainly present in human saliva. The last two groups have random coil conformation in hydrophilic environments and α-helices in a hydrophobic environment.
TL;DR: In this article, a recombinant version of LL37 loaded into chitosan nanoparticles (CSNPs) was used for wound healing and elimination of MRSA infection.
Abstract: Antimicrobial peptides have illustrated potent abilities in the elimination of several pathogens resistant to conventional antimicrobial therapeutic agents. LL37 is a well-known human-originated antimicrobial peptide with significant antibacterial activities. Chitosan is considered as an antimicrobial and biodegradable polymer with various therapeutic applications. This study aimed to produce recombinant LL37 loaded into chitosan nanoparticles (CSNPs). So, the synthetic gene of LL37 was cloned into the pET32a expression vector and E. coli BL21 was used as expression host. The antimicrobial performance of the produced recombinant LL37 was analyzed using minimum inhibitory concentration test. Chitosan-LL37 nanoparticles (CSLL37NPs) and blank CSNPs were prepared through the ionic gelation method with TPP crosslinking. The DLS and FE-SEM results confirmed the preparation of spherical CSLL37NPs with an average size of 127.12 nm. The encapsulation efficiency was 78.52%. The encapsulation improved the peptide antimicrobial activity and enhanced stability under thermal, salts, and acidic pH treatments. The more efficient effects of CSLL37NPs on the wound healing progress and elimination of MRSA infection were proved by in vivo assay. Thus, nano-encapsulation of LL37 by chitosan exacerbates its antimicrobial effects and significantly improves the wound-healing capabilities of free LL37.
TL;DR: This exploratory study was conducted to commence the investigation for crafting multi target epitope vaccine against its bacterial pathogen Tropheryma whipplei, and leads in the prediction of two epitopes: VLMVSAFPL and IRYLAALHL interacting with 4 and 6 HLA DRB1 alleles of MHC Class II respectively.
Abstract: Whipple's disease is one of the rare maladies in terms of spread but very fatal one as it is linked with many disorders (like Gastroenteritis, Endocarditis etc.). Also, current regimens include less effective drugs which require long duration follows up. This exploratory study was conducted to commence the investigation for crafting multi target epitope vaccine against its bacterial pathogen Tropheryma whipplei. The modern bioinformatics tools like VaxiJen, NETMHCII PAN 3.2, ALLERGEN-FP, PATCH-DOCK, TOXIC-PRED, MHCPRED and IEDB were deployed, which makes the study more intensive in analyzing proteome of T. whipplei as these methods are based on robust result generating statistical algorithms ANN, HMM, and ML. This Immuno-Informatics approach leads us in the prediction of two epitopes: VLMVSAFPL and IRYLAALHL interacting with 4 and 6 HLA DRB1 alleles of MHC Class II respectively. VLMVSAFPL epitope is a part of DNA-directed RNA polymerase subunit beta, and IRYLAALHL epitope is a part of membranous protein insertase YidC of this bacterium. Molecular-Docking and Molecular-Simulation analysis yields the perfect interaction based on Atomic contact energy, binding scores along with RMSD values (0 to 1.5 Ǻ) in selection zone. The IEDB (Immune epitope database) population coverage analysis exhibits satisfactory relevance with respect to world population.
TL;DR: In this article, the authors investigated the interaction of coomassie brilliant blue G-250 (CBBG-250) with bovine serum albumin (BSA) by multispectroscopic methods.
Abstract: Aim of present study was to investigate the interaction of coomassie brilliant blue G-250 (CBBG-250) with bovine serum albumin (BSA) by the multispectroscopic methods. Fluorescence-data showed that the complex of BSA-CBBG-250 forming made the intrinsic fluorescence quenching of BSA by CBBG-250 interaction. BSA also could interact with CBBG-250 and the CBBG-BSA complexes formed in a molar ratio of 1:1. UV–Vis results displayed that the apparent binding (association) constant Ka of CBBG-250 with BSA was 5.03 × 104 (298 K), 3.04 × 104 (303 K), 2.84 × 104 (308 K) and 1.99 × 104 (313 K) L mol−1 at different temperatures, respectively. The enthalpy change (△H) and entropy change (△S) were respectively calculated to be − 45.32 kJ mol−1 and − 139.18 J mol−1 K−1, indicating that the hydrogen bonds and Van der Waals forces played dominant roles in the interaction. The results showed that the diphenylamine structure and amino acid residues in the Coomassie Brilliant Blue G-250 had a strong Van der Waals force. The phenyl sulphonic acid group undergoes electrostatic interactions and hydrogen bond interactions with basic amino acids; the compound Coomassie Brilliant Blue G-250 can form a stable complex with BSA.
TL;DR: In this paper, the potential of peptides from quinoa seed proteins as multi-target antagonists against SARS-CoV-2 spike glycoprotein receptor-binding domain, main protease, and papain-like protease was investigated.
Abstract: Peptides are promising antagonists against severe acute respiratory syndrome coronavirus type 2 (SARS-CoV-2). To expedite drug discovery, a computational approach is widely employed for the initial screening of anti-SARS-CoV-2 candidates. This study aimed to investigate the potential of peptides from quinoa seed proteins as multi-target antagonists against SARS-CoV-2 spike glycoprotein receptor-binding domain, main protease, and papain-like protease. Five quinoa proteins were hydrolyzed in silico by papain and subtilisin. Among the 1465 peptides generated, seven could interact stably with the key binding residues and catalytic residues of the viral targets, mainly via hydrogen bonds and hydrophobic interactions. The seven peptides were comparable or superior to previously reported anti-SARS-CoV-2 peptides based on docking scores. Key residues in the seven peptides contributing to binding to viral targets were determined by computational alanine scanning. The seven peptides were predicted in silico to be non-toxic and non-allergenic. The peptides ranged between 546.66 and 3974.87 g/mol in molecular mass, besides exhibiting basic and cationic properties (isoelectric points: 8.26–12.10; net charges: 0.1–4.0). Among the seven peptides, VEDKGMMHQQRMMEKAMNIPRMCGTMQRKCRMS was found to bind the largest number of key residues on the targets. In conclusion, seven putative non-toxic, non-allergenic, multi-target anti-SARS-CoV-2 peptides were identified from quinoa seed proteins. The in vitro and in vivo efficacies of the seven peptides against SARS-CoV-2 deserve attention in future bench-top testing.
TL;DR: The genome analysis and in silico studies suggest that Bacillus aryabhattai could be explored for the production and characterization of biosurfactants relevant to the biopharmaceutical industry.
Abstract: Biosurfactants such as lipopeptides, lipoketides, and peptides produced by Bacillus species exhibit antimicrobial properties. In the present study, genome analysis was carried out to identify the possible lipopeptides produced by the bacterial strain of Bacillus aryabhattai. Iturin A, Surfactin A, Syringomycin E, Bacitracin A, Tryrocidine A, and Fengycin were identified as the possible lipopeptides produced by Bacillus aryabhattai. The identified lipopeptides were further studied by the application of in silico drug discovery tools like molecular docking and molecular dynamics. The target (1,3)-β-D-glucan synthase from Candida albicans was selected. The molecular docking studies showed that Iturin A revealed the best binding affinity against the target with the binding energy of −10.4 kcal/mol. The complex of (1,3)-β-D-glucan synthase- Iturin A was further subjected to molecular dynamics simulation under physiological conditions for the duration of 50 ns, and the results showed, ligand conformation during the simulation stayed close to original conformation state. The genome analysis and in silico studies suggest that Bacillus aryabhattai could be explored for the production and characterization of biosurfactants relevant to the biopharmaceutical industry.
TL;DR: This work focuses on the recent advances in the isolation of tumor-targeting peptides by biopanning methods, with particular emphasis on molecular imaging, and pharmaceutical targeting therapy.
Abstract: Phage display is an effective and powerful technique that provides a route to discovery unique peptides targeting to tumor cells. Specifically binding peptides are considered as the valuable target directing molecule fragments with potential efficiency to improve the current tumor clinic, and offer new approaches for tumor prevention, diagnosis and treatment. We focus on the recent advances in the isolation of tumor-targeting peptides by biopanning methods, with particular emphasis on molecular imaging, and pharmaceutical targeting therapy.
TL;DR: The present study aims to identify potent vaccine peptide candidates against bap AB protein in A.baumannii involved with the biofilm associated virulence using immune informatics approach and predictions as non-toxic, probable, soluble and stable antigens for vaccine design.
Abstract: The present study is aimed to identify potent vaccine peptide candidates against bapAB protein in A.baumannii involved with the biofilm associated virulence using immune informatics approach. FASTA sequence of the bapAB protein from A.baumannii was subjected to assess druggability, physico-chemical analysis, IEDB T-cell mapping, class-1 immunogenicity, conservancy and toxigenicity evaluations together with class-II epitope predictions. Final selection of B-cell epitopes was done with IEDB B-cell epitope tool and final docking of the peptides were interpreted by hydrogen bonds and interaction scores with TLR-2. Promising scores on antigenicity, GRAVY, instability and aliphatic index were obtained. Based on the combinatorial scores, 9 peptides (20aa) were selected on the positive scores of class-I immunogenicity and 7 peptides possessed > 50% class-I conservancy. Class-II conservancy yielded 5 epitopes (E1-E5) with > 50% conservancy with final predictions as non-toxic, probable, soluble and stable antigens for vaccine design. Galaxy WEBDock with TLR-2 receptor showed promising interactions for all epitopes with E2 and E3 possessing a maximum hydrogen bond interactions (n = 13) followed by E1.
TL;DR: In this paper, a multi-objective approach using desirability function generated through predictor importance and weighted coefficient methodology was adopted for optimization of Bioprocess nutritional conditions for production of glutaminase-near free L-asparaginase by Aspergillus candidus UCCM 00117 was conducted under shake flask laboratory conditions.
Abstract: Sequential optimization of bioprocess nutritional conditions for production of glutaminase-near-free L-asparaginase by Aspergillus candidus UCCM 00117 was conducted under shake flask laboratory conditions. Catalytic and anti-cancer activities of the poly-peptide were evaluated using standard in vitro biochemical methods. Medium nutrients were selected by one-factor-at-a-time (OFAT) approach while Plackett–Burman design (PBD) screened potential factors for optimization. Path of steepest ascent (PSA) and response surface methodology (RSM) of a Min-Run-Res V fractional factorial of a central composite rotatable design (CCRD) were employed to optimize factor levels towards improved enzyme activity. A multi-objective approach using desirability function generated through predictor importance and weighted coefficient methodology was adopted for optimization. The approach set optimum bioprocess conditions as 49.55 g/L molasses, 64.98% corn steep liquor, 44.23 g/L asparagine, 1.73 g/L potassium, 0.055 g/L manganese and 0.043 g/L chromium (III) ions, at a composite desirability of 0.943 and an L-asparaginase activity of 5216.95U. The Sephadex-200 partially-purified polypeptide had a specific activity of 476.84 U/mg; 0.087U glutaminase activity, 36.46% yield and 20-fold protein purification. Anti-cancer activity potentials of the catalytic poly-peptide were dose-dependent with IC50 (µg/mL): 4.063 (HL-60), 13.75 (HCT-116), 15.83 (HeLa), 11.68 (MCF-7), 7.61 (HepG-2). The therapeutic enzyme exhibited 15-fold more cytotoxicity to myeloid leukemia cell line than to normal (HEK 238 T) cell. Optimum temperature and pH for activity were within physiological range. However, significant interactions between exposure time and levels of each of temperature and pH made interpretations of residual enzyme activities difficult. The manganese-dependent L-asparaginase from Aspergillu s candidus UCCM 00117 is recommended for further anticancer drug investigations.
TL;DR: The VMH is the first satiety center in the brain, and it receives various inputs from different regions of the brain and circulation via multiple receptors, as well as integrating these inputs and sending the appropriate output to other areas of thebrain, VMH plays an important role in central control of food intake.
Abstract: Hypothalamus is the most critical center in the brain for regulation of food intake. Hypothalamus performs this function through special nuclei. The most important of these nuclei is PVN, because in addition to receiving input from special hypothalamic nuclei, it also receives input from other regions of the brain, as well circulation. Inputs received from other areas of the brain via special receptors including: MCR, GABA, IR, LepR, CBR, OXR, HR, NPY, D, CRF, and GHSR. Due to the presence of several receptors on VMH, different neurotransmitters and neuromodulators related to central food intake regulation effect on this nucleus. These neurotransmitters include two categories: orexigenic and anorexigenic. Orexigenic neuropeptides such as: NPY, orexin, endocannabinoids, glutamate, urocortin, and ghrelin. Anorexigenic neuropeptides included: MSH, CRF, leptin, insulin, BDNF, histamine, and dopamine. Then, VMH integrates these inputs from the bind of these neurotransmitters to their receptors, and sends the final feedback to other brain regions. The VMH is the first satiety center in the brain, and it receives various inputs from different regions of the brain and circulation via multiple receptors, as well as integrating these inputs and sending the appropriate output to other areas of the brain, VMH plays an important role in central control of food intake. Therefore, throughout this review article would discuss the function of this nucleus on central regulation of food intake via various neuropeptides and receptors.
Legend: ARC: Arcuate nucleus. PVN: Paraventricular nucleus. VMH: Ventromedial hypothalamus. SF1: Serotonergic factor 1. BDNF: Brain-derived neurotropic factor. POMC: pro-opiomelanocortin. AgRP/NPY: Agouti related protein/ Neuropeptide Y. VTA: Ventral tegmental area. CB: Endocannabinoidergic neuron. OX: Orexin neuron. TB: Tuberommillary nucleus. H: Histaminergic neuron. D: Dopaminergic neuron. G: Glutamatergic neuron.: Stimulatory projection.: Inhibitory projection.
TL;DR: This study provided an effective prediction for GSTs based on the concept of PseAAC and four different machine learning algorithms using Chou’s pseudo-amino acid composition concept.
Abstract: The Glutathione S-Transferases (GSTs) are detoxification enzymes which exist in variety of living organisms such as bacteria, fungi, plants and animals. These multifunctional enzymes play important roles in the biosynthesis of steroids, prostaglandins, apoptosis regulation, and stress signaling. In this study, we designed a method to independently predict the structures of animal, fungal and plant GSTs using Chou’s pseudo-amino acid composition concept. Support vector machine (SVM), Random Forests (RF), Covariance Discrimination (CD) and Optimized Evidence-Theoretic K-nearest Neighbor (OET-KNN) were used as powerful machine learnings algorithms. Based on our results, Random Forests demonstrated the best prediction for animal GSTs with 0.9339 accuracy and SVM showed the best results for fungal and plant GSTs with 0.8982 and 0.9655 accuracy, respectively. Our study provided an effective prediction for GSTs based on the concept of PseAAC and four different machine learning algorithms.
TL;DR: In this paper, the SARS-CoV-2 Mpro inhibitory activity of di- and tri-peptides (DTPs) resulted from the proteolysis of bovine milk proteins was evaluated.
Abstract: Viruses of the picornavirus-like supercluster mainly achieve cleavage of polyproteins into mature proteins through viral 3-chymotrypsin proteases (3Cpro) or 3-chymotrypsin-like proteases (3CLpro). Due to the essential role in processing viral polyproteins, 3Cpro/3CLpro is a drug target for treating viral infections. The 3CLpro is considered the main protease (Mpro) of coronaviruses. In the current study, the SARS-CoV-2 Mpro inhibitory activity of di- and tri-peptides (DTPs) resulted from the proteolysis of bovine milk proteins was evaluated. A set of 326 DTPs were obtained from virtual digestion of bovine milk major proteins. The resulted DTPs were screened using molecular docking. Twenty peptides (P1–P20) showed the best binding energies (ΔGb < − 7.0 kcal/mol). Among these 20 peptides, the top five ligands, namely P1 (RVY), P3 (QSW), P17 (DAY), P18 (QSA), and P20 (RNA), based on the highest binding affinity and the highest number of interactions with residues in the active site of Mpro were selected for further characterization by ADME/Tox analyses. For further validation of our results, molecular dynamics simulation was carried out for P3 as one of the most favorable candidates for up to 100 ns. In comparison to N3, a peptidomimetic control inhibitor, high stability was observed as supported by the calculated binding energy of the Mpro-P3 complex (− 59.48 ± 4.87 kcal/mol). Strong interactions between P3 and the Mpro active site, including four major hydrogen bonds to HIS41, ASN142, GLU166, GLN189 residues, and many hydrophobic interactions from which the interaction with CYS145 as a catalytic residue is worth mentioning. Conclusively, milk-derived bioactive peptides, especially the top five selected peptides P1, P3, P17, P18, and P20, show promise as an antiviral lead compound.
TL;DR: The designed multi-epitopic vaccine was assessed for antigenicity, allergenicity and various physiochemical parameters and was validated to be highly immunogenic and can serve as a valuable proactive remedy for subject pathogens.
Abstract: Klebsiella pneumoniae and Mycobacterium tuberculosis coinfection is one of the most lethal combinations that has been becoming frequent yet, not diagnosed and reported properly. Due to the simultaneous occurrence of both infections, diagnosis is delayed leading to inadequate treatments and mortality. With the rise of MDR Klebsiella and Mycobacterium, a prophylactic and an immunotherapeutic vaccine has to be entailed for preemptive and adroit therapeutic approach. In this study, we aim to implement reverse vaccinology approach that encompasses a comprehensive evaluation of vital aspects of the pathogens to explore immunogenic epitopes against Omp A of Klebsiella and Rv1698, Rv1973 of Mtb that may help in vaccine development. The designed multi-epitopic vaccine was assessed for antigenicity, allergenicity and various physiochemical parameters. Molecular docking and simulations were executed to assess the immunogenicity and complex stability of the vaccine. The final multi-epitopic vaccine is validated to be highly immunogenic and can serve as a valuable proactive remedy for subject pathogens.
TL;DR: Analysis showed that VK2 multi-epitope vaccine could be a suitable target to control the K. pneumoniae infections.
Abstract: Klebsiella pneumoniae is a Gram-negative opportunistic pathogen that causes bacteremia, meningitis, endocarditis, cellulitis, urinary tract infections. The emergence of antibiotic resistance in this pathogen makes the infection of K. pneumoniae more dangerous. Therefore, it is the need of hour to use the advanced technologies for developing vaccines, which can surpass the traditional methods used for treating the infections. In our study, we have considered designing multi-epitope based vaccines targeting the outer membrane proteins of K. pneumoniae. The proteome of K. pneumoniae was analysed using subtractive proteomics, and reverse vaccinology. In subtractive proteomics, the proteins were sorted on the basis of SignalP, TatP, LIPOP, Transmembrane helicity (TMHMM, HMMTOP), and cellular localization (CELLO and PSORTb). Fifteen outer membrane protein were selected that had the potential for the multi-epitope based vaccine designing. The MHC I, MHC II, B cell interacting epitopes of these proteins, which could generate a decent cellular and humoral immune responses in the host cell, were analysed. On this basis, four vaccine constructs (VK1 to VK4) were analyzed for their antigenicity, allergenicity, solubility, and physicochemical properties. Out of these constructs, VK2 was modeled using RapotorX server and docked (PatchDock) with different HLA alleles, and its molecular dynamics was also studied. These analysis showed that VK2 multi-epitope vaccine could be a suitable target to control the K. pneumoniae infections.
TL;DR: This review covers 25 FDA-approved peptide drugs up to 20 residues in length and details their metabolic and degradation pathways in the human body after administration.
Abstract: Although peptide drugs make up only about 2% of all drugs approved by the United States Food and Drug Administration (FDA), they play important roles in the treatment of certain diseases where no small molecule drugs or therapeutic antibodies can fulfil. A primary reason for the strong preference of small molecules over peptides is the latter’s susceptibility to degradation by human proteases, resulting in very short systemic half-lives. To circumvent this, peptide chemists have resorted to introducing unnatural amino acids and chemical modifications to enhance their metabolic stabilities. Hence, understanding how peptide drugs are metabolized by the human body will help in the design of more stable peptide drugs. This review covers 25 FDA-approved peptide drugs up to 20 residues in length and details their metabolic and degradation pathways in the human body after administration.
TL;DR: The role of major regulators and their mediatory interactions with one another in poultry feeding behavior is investigated and it seems that dopamine, serotonin, and glutamate play an axial role in the central regulation of food intake in CNS.
Abstract: Appetite is controlled by a complex system of central and peripheral signals interacting to modulate the ingestion response. Several brain mediators with complex networks adjust food intake in birds. Based on the available literature, these mediators have interactions with a number of other neurotransmitters (NTS) involved in feed intake. It means that, NTS regulate feeding behavior through mediating other peptide and NTs activity. In birds, insulin known as a hypophagic hormone that is interplaying with neuropeptide Y (NPY), pro-opiomelanocortin (POMC), and corticotropin-releasing factor (CRF) in brain. Another hormone ghrelin, inhibits food intake in birds and other mediators, such as glutamate, endocannabinoid system (ECS), serotonin (5-hydroxytryptamine, 5-HT), and norepinephrine (NE), which play a key role in ghrelin-induced hypophagia. Another involved peptide on feeding behavior in chickens called nociceptin/orphanin FQ (N/OFQ) is modulated by histamine, glutamate, dopamine (DA), gamma-aminobutyric acid (GABA), agouti-related protein (AgRP), and cocaine and amphetamine-regulated transcript (CART). Some of the NTS such as opioid have both orexigenic and anorexigenic effects in birds while has interaction with NE, glutamate, histamine, DA, and cannabinoids (CBs). Thus, interaction among mediators is a prominent process needs to be considered in order to understanding the mechanisms underlying feed intake regulation in birds. This review aims to investigate the role of major regulators and their mediatory interactions with one another in poultry feeding behavior. According to mentioned interactions, it seems that dopamine, serotonin, and glutamate have the most interactions with other NT systems. Therefore, they play an axial role in the central regulation of food intake in CNS.
TL;DR: This study developed a support vector machine (SVM) based model to accurately identify DPP-IV inhibitory peptides and showed that the proposed method achieved significant improvement in classification performance, as compared with the existing method.
Abstract: Dipeptidyl peptidase-IV (DPP-IV) inhibitory peptides play a crucial role in drug development and the treatment of diabetes. Thus, it is an urgent task to fast and precise distinguishing DPP-IV inhibitory peptides from non-DPP-IV inhibitory peptides. This study developed a support vector machine (SVM) based model to accurately identify DPP-IV inhibitory peptides. Specifically, the peptide sequences were firstly encoded by fifty kinds of physicochemical properties, and dynamic time warping algorithm was introduced to capture the correlation information of distinct physicochemical properties of amino acids. To further remove the effect of noise, orthogonal minimum spanning tree algorithm was proposed. Finally, the features were inputted into SVM to discriminate DPP-IV from non-DPP-IV inhibitory peptides. In the jackknife test, our proposed method achieved 86.28% and 87.97% classification accuracies on benchmark and independent datasets, respectively. The experimental results showed that the proposed method achieved significant improvement in classification performance, as compared with the existing method. The datasets and code are publicly available at https://figshare.com/articles/online_resource/iDPPIV/14769174
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