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Purpose: Enterovirus 71, a pathogen that causes hand-foot and mouth disease (HFMD) is currently regarded as an increasing neurotropic virus in Asia and can cause severe complications in pediatric patients with blister-like sores or rashes on the hand, feet, and mouth. Notwithstanding the significant burden of the disease, no authorized vaccine is available. Previously identified attenuated and inactivated vaccines are worthless over time owing to changes in the viral genome. Materials and Methods: A novel vaccine construct using B-cell derived T-cell epitopes from the virulent polyprotein found the induction of possible immune response. In order to boost the immune system, a beta-defensin 1 preproprotein adjuvant with EAAAK linker was added at the N-terminal end of the vaccine sequence. Results: The immunogenicity of the designed, refined, and verified prospective threedimensional-structure of the multi-epitope vaccine was found to be quite high, exhibiting nonallergenic and antigenic properties. The vaccine candidates bound to toll-like receptor 3 in a molecular docking analysis, and the efficacy of the potential vaccine to generate a strong immune response was assessed through in silico immunological simulation. Conclusion: Computational analysis has shown that the proposed multi-epitope vaccine is possibly safe for use in humans and can elicit an immune response. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus has been widely reported to be majorly responsible for causing nosocomial infections worldwide. Due to an increase in antibiotic‐resistant strains, the development of an effective vaccine against the bacteria is the most viable alternative. Therefore, in the current work, an effort has been undertaken to develop a novel peptide‐based vaccine construct against S aureus that can potentially evoke the B and T cell immune responses. The fibronectin‐binding proteins are an attractive target as they play a prominent role in bacterial adherence and host cell invasion and are also well conserved among rapidly mutating pathogens. Therefore, highly immunogenic linear B lymphocytes (LBL), cytotoxic T lymphocytes (CTL), and helper T lymphocytes (HTL) epitopes were identified from the antigenic fibronectin‐binding proteins A and B (FnBPA and FnBPB) of S aureus using immunoinformatics approaches. The selected peptides were confirmed to be non‐allergenic, non‐toxic, and with a high binding affinity to the majority of human leukocyte antigens (HLA) alleles. Consequently, the multi‐peptide vaccine construct was developed by fusing the screened epitopes (three LBL, five CTL, and two HTL) together with the suitable adjuvant and linkers. In addition, the tertiary conformation of the peptide construct was modeled and later docked to the Toll‐like receptor 2. Subsequently, a molecular dynamics simulation of 100 ns was employed to corroborate the stability of the designed vaccine‐receptor complex. Besides exhibiting high immunogenicity and conformational stability, the developed vaccine was observed to possess wide population coverage of 99.51% worldwide. Additional in vivo and in vitro validation studies would certainly corroborate the designed vaccine construct to have improved prophylactic efficacy against S aureus. Staphylococcus aureus is a major cause of nosocomial infections worldwide, and the development of an effective vaccine against it is the most viable alternative. This work has been undertaken to develop a novel peptide‐based vaccine construct against S. aureus that can evoke the B and T cell immune responses. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is a human bacterial pathogen that can cause a wide range of symptoms. As virulent and multi-drug-resistant strains of S. aureus have evolved, invasive S. aureus infections in hospitals and the community have become one of the leading causes of mortality and morbidity. The development of novel techniques is therefore necessary to overcome this bacterial infection. Vaccines are an appropriate alternative in this context to control infections. In this study, the collagen-binding protein (CnBP) from S. aureus was chosen as the target antigen, and a series of computational methods were used to find epitopes that may be used in vaccine development in a systematic way. The epitopes were passed through a filtering pipeline that included antigenicity, toxicity, allergenicity, and cytokine inducibility testing, with the objective of identifying epitopes capable of eliciting both T and B cell-mediated immune responses. To improve vaccine immunogenicity, the final epitopes and phenol-soluble modulin α4 adjuvant were fused together using appropriate linkers; as a consequence, a multiepitope vaccine was developed. The chosen T cell epitope ensemble is expected to cover 99.14% of the global human population. Furthermore, docking and dynamics simulations were used to examine the vaccine's interaction with the Toll-like receptor 2 (TLR2), revealing great affinity, consistency, and stability between the two. Overall, the data indicate that the vaccine candidate may be extremely successful, and it will need to be evaluated in experimental systems to confirm its efficiency. [ABSTRACT FROM AUTHOR]

• In silico drug discovery approach from plant derived secondary metabolites. • Target identification from type 3 fimbrial protein of K. pneumoniae. • Molecular docking to identify the interaction between target protein and screened ligand. • Vernolide compound has shown the potential to inhibit the pneumonia infection. • MD simulation revealed structural and conformational changes associated with the binding of identified inhibitor. Klebsiella pneumoniae is an important multidrug-resistant pathogen affecting humans and a major source for hospital infections associated with high morbidity and mortality due to limited treatment options. The pathogenesis of this microbe is caused by several key proteins; one of them is type 3 fimbrial proteins, which has been known for its crucial role in the host cell invasion. Therefore, targeting fimbriae protein can be a solution for treating this pathogenic disease. Plant Secondary metabolites with diverse chemical scaffolds have been recognized as an invaluable source of compounds in drug discovery and development. However, systematic identification of drug targets for plant secondary metabolites at the human proteome level via various experimental assays is highly expensive and time-consuming. In this study, we have employed plant derived secondary metabolites to predict new drug targets of type 3 fimbrial protein of K. pneumoniae. Subsequently, structure-based virtual screening was performed to identify compounds showing the best binding confirmation with the target enzyme and forming a stable complex. Molecular dynamics simulations of the protein-ligand complex indicated that the intermolecular hydrogen bonds formed between the protein and ligand complex remain stable during the simulation time. The interaction shown by the compounds provides an important insight into the mechanism involved in the ligand-receptor interaction. The model will aid in the development of a drug with improved efficacy and reduced side effects. Thus, vernolide could serve as a drug for treating pneumonia infections in humans. The drug likeliness prediction on this derivative also supports its suitability as a drug candidate. However, an in vitro and in viv o analysis of the selected compound is necessary for further validation before administration of the drug to human beings. [ABSTRACT FROM AUTHOR]

COVID-19 is a systemic disease affecting multiple organ systems and caused by infection with the SARS-CoV-2 virus. Two years into the COVID-19 pandemic and after the introduction of several vaccines, the pandemic continues to evolve in part owing to global inequities in access to preventive and therapeutic measures. We are also witnessing the introduction of antivirals against COVID-19. Against this current background, we review the progress made with nanotechnology-based approaches such as nanoformulations to combat the multiorgan effects of SARS-CoV-2 infection from a systems medicine lens. While nanotechnology has previously been widely utilized in the antiviral research domain, it has not yet received the commensurate interest in the case of COVID-19 pandemic response strategies. Notably, SARS-CoV-2 and nanomaterials are similar in size ranging from 50 to 200 nm. Nanomaterials offer the promise to reduce the side effects of antiviral drugs, codeliver multiple drugs while maintaining stability in the biological milieu, and sustain the release of entrapped drug(s) for a predetermined time period, to name but a few conceivable scenarios, wherein nanotechnology can enable and empower preventive medicine and therapeutic innovations against SARS-CoV-2. We conclude the article by underlining that nanotechnology-based interventions warrant further consideration to enable precision planetary health responses against the COVID-19 pandemic. [ABSTRACT FROM AUTHOR]

Klebsiella pneumoniae is an emerging human pathogen causing neonatal lung disease, catheter-associated infections, and nosocomial outbreaks with high fatality rates. Capsular polysaccharide (CPS) protein plays a major determinant in virulence and is considered as a promising target for vaccine development. In this study, we used immunoinformatic approaches to design a multi-peptide vaccine against K. pneumonia. The epitopes were selected through several immune filters, such as antigenicity, conservancy, nontoxicity, non-allergenicity, binding affinity to HLA alleles, overlapping epitopes, and peptides having common epitopes. Finally, a construct comprising 2 B-Cell, 8 CTL, 2 HTL epitopes, along with adjuvant, linkers was designed. Peptide-HLA interaction analysis showed strong binding of these epitopes with several common HLA molecules. The in silico immune simulation and population coverage analysis of the vaccine showed its potential to evoke strong immune responses.. Further, the interaction between vaccine and immune was evaluated by docking and simulation, revealing high affinity and complex stability. Codon adaptation and in silico cloning revealed higher expression of vaccine in E. coli K12 expression system. Conclusively, the findings of the present study suggest that the designed novel multi-epitopic vaccine holds potential for further experimental validation against the pathogen. [ABSTRACT FROM AUTHOR]

Waste from the fruit industry is the main source of pectin, which has a huge global market. Pectinolytic enzymes produced from bacteria have been widely used in the fruit and vegetable processing industry to break down pectic substances. Pectate lyase from mesophilic, thermophilic, and psychrophilic organisms are investigated using in-silico methods, as well as comparative docking with Pectin substrate are reported in this study, order to develop a permissive agent for agro-waste/food waste treatment. The total number of 18 bacterial protein sequences was chosen based on their potential for substantial uses in agro-waste treatment. Functional phylogenetic analysis revealed three distinct groups, each split by several maximum likelihoods. Motif elicitation among the selected Pectate lyase sequences revealed five motifs with widths ranging from 100 to 200. Physicochemical characterization indicates the low hydrophobic nature of Pectate lyase and the possibility of stability at a wide range of temperatures. Docking experiments Pectate lyase from Saccharophagus degradans showed stronger affinity for the substrate and better energy efficiency than Bacillus coagulans or Sphingopyxis bauzanensis. To summarize, we posited that pectate lyase from mesophilic bacteria might offer significant benefits over its counterparts. In fact, further experimentation is required to determine their effective usage in distinct food industries. [ABSTRACT FROM AUTHOR]

[Display omitted] • Type 3 fimbrial protein (mrkA) protein plays a major determinant in the virulence of K. pneumoniae. • Immunoinformatic approaches was employed to design a novel multi-peptide vaccine to induce humoral and cellular immune responses. • Immunological potential including the allergenicity, antigenicity, non-toxicity, and population coverage analysis of the construct were also evaluated. • Molecular docking and MD simulation exhibited a strong and stable binding affinity between vaccine-TLR2. Pneumonia is a major endemic disease around the world, and an effective vaccine is the need of the hour to fight against the disease. When there are no appropriate antiviral and associated therapies available, vaccine development becomes even more essential. Therefore, in the present study, a variety of immunoinformatics techniques was utilized to develop a novel multi-epitope vaccine that targets the highly immunodominant type 3 fimbrial protein of Klebsiella pneumoniae, the causal organism for pneumonia. The putative B and T cell epitopes were predicted from the protein and screened for antigenicity, toxicity, allergenicity, and cross-reactivity with human proteomes. Subsequently, the selected epitopes were joined with the help of linkers to form a robust vaccine construct. In addition, an adjuvant was applied to the N-terminal of the construct to improve the immunogenicity of the vaccine. The physicochemical properties, solubility, the secondary and tertiary structure of the final vaccine were also established. MD simulations for 100 ns were employed to assess the stability of the vaccine-TLR-2 docked complex. The final vaccine was optimized and cloned in pET28a (+) vector with His-tag to achieve maximum vaccine protein expression for ease of purification. Immune simulation results indicated the potency of this vaccine candidate as a probable therapeutic agent. In conclusion, the overall results of various immunoinformatics tools and methods employed revealed that the constructed multi-epitope vaccine exhibits a high potential for stimulating both B and T-cells immune responses against pneumonia infection. However, experimental immunological studies are required to corroborate the viability of the novel multi-epitope construct as a commercial vaccine. [ABSTRACT FROM AUTHOR]

Staphylococcus aureus is one of the most notorious Gram-positive bacteria with a very high mortality rate. The WHO has listed S. aureus as one of the ESKAPE pathogens requiring urgent research and development efforts to fight against it. Yet there is a major layback in the advancement of effective vaccines against this multidrug-resistant pathogen. SdrD and SdrE proteins are attractive immunogen candidates as they are conserved among all the strains and contribute specifically to bacterial adherence to the host cells. Furthermore, these proteins are predicted to be highly antigenic and essential for pathogen survival. Therefore, in this study, using the immunoinformatics approach, a novel vaccine candidate was constructed using highly immunogenic conserved T-cell and B-cell epitopes along with specific linkers, adjuvants, and consequently modeled for docking with human Toll-like receptor 2. Additionally, physicochemical properties, secondary structure, disulphide engineering, and population coverage analysis were also analyzed for the vaccine. The constructed vaccine showed good results of worldwide population coverage and a promising immune response. For evaluation of the stability of the vaccine-TLR-2 docked complex, a molecular dynamics simulation was performed. The constructed vaccine was subjected to in silico immune simulations by C-ImmSim and Immune simulation significantly provided high levels of immunoglobulins, T-helper cells, T-cytotoxic cells, and INF-γ. Lastly, upon cloning, the vaccine protein was reverse transcribed into a DNA sequence and cloned into a pET28a (+) vector to ensure translational potency and microbial expression. The overall results of the study showed that the designed novel chimeric vaccine can simultaneously elicit humoral and cell-mediated immune responses and is a reliable construct for subsequent in vivo and in vitro studies against the pathogen. [ABSTRACT FROM AUTHOR]

Microalgae are potential feedstocks for the commercial production of carotenoids, however, the metabolic pathways for carotenoid biosynthesis across algal lineage are largely unexplored. This work is the first to provide a comprehensive survey of genes and enzymes associated with the less studied methylerythritol 4-phosphate/1-deoxy-D-xylulose 5-phosphate pathway as well as the carotenoid biosynthetic pathway in microalgae through bioinformatics and comparative genomics approach. Candidate genes/enzymes were subsequently analyzed across 22 microalgae species of lineages Chlorophyta, Rhodophyta, Heterokonta, Haptophyta, Cryptophyta, and known Arabidopsis homologs in order to study the evolutional divergence in terms of sequence-structure properties. A total of 403 enzymes playing a vital role in carotene, lutein, zeaxanthin, violaxanthin, canthaxanthin, and astaxanthin were unraveled. Of these, 85 were hypothetical proteins whose biological roles are not yet experimentally characterized. Putative functions to these hypothetical proteins were successfully assigned through a comprehensive investigation of the protein family, motifs, intrinsic physicochemical features, subcellular localization, pathway analysis, etc. Furthermore, these enzymes were categorized into major classes as per the conserved domain and gene ontology. Functional signature sequences were also identified which were observed conserved across microalgal genomes. Additionally, the structural modeling and active site architecture of three vital enzymes, DXR, PSY, and ZDS catalyzing the vital rate-limiting steps in Dunaliella salina were achieved. The enzymes were confirmed to be stereochemically reliable and stable as revealed during molecular dynamics simulation of 100 ns. The detailed functional information about individual vital enzymes will certainly help to design genetically modified algal strains with enhanced carotenoid contents., (© 2021. The Author(s), under exclusive licence to Springer Nature B.V.)