Vaccines are widely used worldwide to prevent and protect from various infections. A variety of modern approaches to developing prophylactic and therapeutic vaccines is growing. In almost all cases, adjuvants are necessary to obtain an effective immune response.This work investigated the possibility of using the pharmaceutical peptide drug Stemokin as an adjuvant stimulating a balanced Th1/Th2 response.A study was conducted to compare the activity of Stemokin versus the approved adjuvant Alhydrogel in a murine vaccination model with the approved VAXIGRIP® vaccine.The first proof-of-concept experimental study shows that the peptide Ile-Glu-Trp has the adjuvant vaccine properties and anti-HA IgG2a enhancing response, revealing a Th1- favoring balanced Th1/Th2 immunomodulation.

Different SARS-CoV-2 new variants emerged and spread during the past few months, sparking infections and death counts. The new variant B.1.617 (delta variant) sparked in India in the past few months, causing the highest records. The B.1.617 variant of SARS-CoV-2 has the double mutations E484Q and L452R on its spike Receptor Binding Domain (RBD). The first mutation is like the reported South African and the Brazilian variants (501.V2 and B.1.1.248). This mutation lies in the region C480-C488, which we predicted before to be recognized by the host-cell receptor; Glucose Regulated Protein 78 (GRP78). In the current study, we test the binding affinity of the host-cell receptor GRP78 to the delta variant spike RBD using molecular docking and molecular dynamics simulations of up to 100 ns. Additionally, the ACE2-RBD is tested by protein-protein docking. The results reveal equal average binding affinities of the GRP78 against wildtype and delta variant spikes. This supports our previous predictions of the contribution of GRP78 in SARS-CoV-2 spike recognition as an auxiliary route for entry.

Non-small-cell lung cancer (NSCLC) is the most common lung cancer which has the highest mortality rate in Indonesia. One of the trends in treating cancer is by utilizing peptide vaccines, an immunotherapeutic approach that aims to stimulate the cell-mediated adaptive immune system to recognize cancer-associated peptides. Currently, no peptide vaccines are available in the market for NSCLC treatment. Therefore, this project aims to develop a multi-epitope peptide-based vaccine for NSCLC utilizing citrullinated peptides. Citrullination is a post-translational modification that occurs in cancer cells during autophagy that functions to induce immune responses towards modified self-epitopes such as tumor cells, through activation of PAD enzymes within the APC and target cells. It was found that introducing a common citrullinated neo-antigen peptide such as vimentin and enolase to the immune system could stimulate a higher specific CD4 T cell response against NSCLC. Moreover, carcinoembryonic antigen (CEA), an antigen that is highly expressed in cancer cells, is also added to increase the vaccine's specificity and to mobilize both CD4 and CD8 T cells. These antigens bind strongly to the MHC Class II alleles such as HLA-DRB1*07:01 and HLA-DRB*11:01, which are predominant alleles in Indonesian populations. Through in silico approach, the peptides generated from CEA, citrullinated vimentin and enolase, were analyzed for their MHC binding strength, immunogenicity, ability to induce IFNγ response, and population coverage. It is expected that the immunodominant antigens presentation is able to induce a potent immune response in NSCLC patients in Indonesia, resulting in tumor eradication.

is one of the leading causes of nosocomial infections, characterized by increasing antibiotic resistance, severity and mortality. Therefore, numerous efforts have been made nowadays to identify new therapeutic targets. This study aimed to find potential drug targets and vaccine candidates in drug-resistant strains of . Extensive antibiotic-resistant and carbapenem-resistant strains of with complete genome were selected and ten common hypothetical proteins (HPs) containing more than 200 amino acids were obtained. The structural, functional and immunological predictions of these HPs were performed with the utility of bioinformatics approaches. Two common HPs (Gene ID: 2877781645 and 2877781936) among other investigated proteins were revealed as potential candidates for pharmaceutical and vaccine purposes based on structural and physicochemical properties, functional domains, subcellular localizations, signal peptides, toxicity, virulence factor, antigenicity, allergenicity and immunoinformatic predictions. The consequence of this predictive study will assist in novel drug and vaccine design through experimental investigations.

Nipah virus (NiV) is an emerging zoonotic virus causing outbreaks of encephalitis and respiratory illnesses in humans, with high mortality. NiV is considered endemic in Bangladesh and Southeast Asia. There are no licensed vaccines against NiV. This study aimed at predicting a dual-antigen multi-epitope subunit chimeric vaccine against surface-glycoproteins G and F of NiV. Targeted proteins were subjected to immunoinformatics analyses to predict antigenic B-cell and T-cell epitopes. The proposed vaccine designs were implemented based on the conservancy, population coverage, molecular docking, immune simulations, codon adaptation, secondary mRNA structure, and in-silico cloning. Total 40 T and B-cell epitopes were found to be conserved, antigenic (vaxijen-value > 0.4), non-toxic, non-allergenic, and human non-homologous. Of 12 hypothetical vaccines, two (NiV_BGD_V1 and NiV_BGD_V2) were strongly immunogenic, non-allergenic, and structurally stable. The proposed vaccine candidates show a negative Z-score (- 6.32 and - 6.67) and 83.6% and 89.3% of most rama-favored regions. The molecular docking confirmed the highest affinity of NiV_BGD_V1 and NiV_BGD_V2 with TLR-4 (ΔG = - 30.7) and TLR8 (ΔG = - 20.6), respectively. The vaccine constructs demonstrated increased levels of immunoglobulins and cytokines in humans and could be expressed properly using an adenoviral-based pAdTrack-CMV expression vector. However, more experimental investigations and clinical trials are needed to validate its efficacy and safety.

The clinical state of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has been considered a pandemic disease (COVID-19) that is rapidly spreading worldwide. Despite all global efforts, the only treatment for COVID-19 is supportive care and there has been no efficient treatment to fight this plague. It is confirmed that patients with chronic diseases such as cardiovascular disorder and diabetes; are more vulnerable to COVID-19. In the severe type of COVID-19, laboratory findings showed a remarkably enhanced C-reactive protein, IL-6 serum, Iron, and ferritin, which suggest an inflammatory response. Inflammation results in iron homeostasis imbalance and causes iron overload, exacerbating the SARSCOV2 infection. More importantly, recent studies have established that SARS-CoV-2 needs iron for viral replication and also activation. As a result, managing iron overload in diabetic patients with COVID-19 could be an early therapeutic approach to limit the lethal inflammatory response of COVID-19. In this review, Deferoxamine (DFO) has been proposed as an effective iron chelator agent.

The current spread of Zika virus infection in India has become a public health issue due to the virus's possible link to birth abnormalities and neurological disorders. There is a need for enhanced vaccines or drugs as a result of its epidemic outbreak and the lack of potential medication. B-cell mediated adaptive immunity is capable of developing pathogen-specific memory that confers immunological protection. Therefore, in this study, the envelope protein of the Zika virus was retrieved from the NCBI protein database. The ABCpred and BepiPred software were used to discover linear B-cell epitopes on envelope protein. Conformational B-cell epitopes on envelope protein were identified using SEPPA 3.0 and Ellipro tools. Predicted B-cell epitopes were evaluated for allergenicity, toxicity, and antigenicity. Two consensus linear B-cell epitopes, envelope (AKVEITPNSPRAEATL) and envelope (PWHAGADTGTPHWNN) were identified using ABCpred and BepiPredtools. SEPPA 3.0 and Elliprotools predicted consensus conformational envelope (DRGWGNGCGLFGK) and envelope (AHAK) epitopes and one residue (PRO) within envelope protein as a component of B-cell epitopes. These predicted linear and conformational B-cell epitopes will help in designing peptide vaccines that will activate the humoral response. However, in-vitro and in-vivo laboratory experimental confirmations are still needed to prove the application's feasibility.

Tuberculosis (TB) is one of the leading cause of death worldwide, and the world is fighting with this global health emergency from the past 25 year. The current clinical interventions for the management of TB face a number of inherent challenges which includes low patient compliance due to the long therapy regimen, and emerging antimicrobial resistance. Therefore, there is an unmet need of new anti-TB therapeutic agent with enhanced safety profile, which can reduce the duration of therapy, enhanced bioavailability and efficacy against drug resistant forms of TB. Bacteriocins or anti microbial peptides (AMPs) occurring in microbes, human beings and other life forms have been investigated as host defense peptides. Structurally AMPs are short and ionized and play crucial role in innate immunity of host. Some AMPs can kill microbial infections directly while others function indirectly by altering the host defense mechanisms. Amidst rising issue of antibiotic resistance, AMPs are being tested in clinical research as potential antibiotics and novel therapeutics to fight against infections and non-infectious diseases. Studies have also highlighted the ability of AMPs to act against the bacteria spreading tuberculosis. The present review provides information on antimicrobial peptides, highlights their biological role, classification and mode of action in treatment and prevention of tuberculosis. It further mentions the prospects and challenges of developing peptides for their therapeutic applications against .

Microbes are helpful and destructive to human health and other living organisms. Microbes can be eliminated by using antibiotics against them, but their capability to resist regularly encountering antibiotics makes them more injurious. Microbes can adjust and adapt according to the chemicals used against them and become antibiotic resistant. Thus, the requirement for novel antimicrobial compounds increases with time to treat antibiotic-resistant microbes. Fish epidermal mucus encounters various pathogens present in their surrounding environment. It has become a rich source of novel antimicrobial compounds mainly antimicrobial peptides that can be used against various antibiotic-resistant pathogenic microbes. Compounds extracted from epidermal mucus can be used synergistically with other antibiotics or resistance modifying agents to inhibit the growth of resistant microbes. Fishes are consumed as a protein-rich food source worldwide and contribute to the world economy. Diseases in fish cause significant losses in the economic benefits exploited by fishermen and industries based on fisheries products. This paper will review compounds from fish epidermal mucus and their use to control the growth of antibiotic-resistant or non-resistant pathogenic microbes of humans and fishes. So, to increase fisheries' economic benefits and decrease infections involving resistant microbes.

Insulin-like growth factor 1 (IGF-1) and its IGF-1 receptor (IGF-1R) belong to an important biological system that is involved in the regulation of normal growth, but that has also been recognized as playing a role in cancer. IGF-1R antagonists could be interesting for the testing of their potential antiproliferative properties as an alternative to IGF-1R tyrosine-kinase inhibitors or anti-IGF-1R monoclonal antibodies. In this study, we were inspired by the successful development of insulin dimers capable of antagonizing insulin effects on the insulin receptor (IR) by simultaneous binding to two separated binding sites and by blocking structural rearrangement of the IR. We designed and produced in three different IGF-1 dimers in which IGF-1 monomers are interlinked through their N- and C-termini, with linkers having 8, 15 or 25 amino acids. We found that the recombinant products were susceptible to the formation of misfolded or reduced variants, but that some of them were able to bind IGF-1R in low nanomolar affinities and all of them activate IGF-1R proportionally to their binding affinities. Overall, our work can be considered as a pilot study that, although it did not lead to the discovery of new IGF-1R antagonists, explored the possibility of recombinant production of IGF-1 dimers and led to the preparation of active compounds. This work could inspire further studies dealing, for example, with the preparation of IGF-1 conjugates with specific proteins for the study of the hormone and its receptor or for therapeutic applications.

Porcine interferon α (poIFN-α) is a crucial cytokine that can prevent and treat viral infections. Seventeen functional porcine IFN-α subtypes were found in the porcine genome. In this study, multiple sequence alignment was performed to analyze IFN-α protein structure and function. Phylogenetic tree analysis of the poIFN gene family defined the evolutionary relationship of various subtypes. PoIFN-αs, including poIFN-α1-17, were expressed in an expression system. The antiviral activities of these IFN-α proteins against vesicular stomatitis virus (VSV) and pseudorabies virus (PRV) were examined in PK-15 cells. We found that the antiviral activity of different poIFN-α molecules greatly differed as follows: the poIFN-α14 and 17 subtypes had the greatest antiviral activities against VSV and PRV in PK-15 cells, poIFN-α1, 2, 3, and 8 exhibited lower biological activities, and poIFN-α4, 5, 6, 7, 9, 10, 11, 12, 13, and 16 had minimal or no effect in the tested target cell‒virus systems. Moreover, our studies demonstrated that the antiviral activity of IFN-α was positively correlated with the induction of IFN-stimulated genes, such as 2'-5' oligoadenylate synthetase 1 (OSA1), interferon-stimulated gene 15 (ISG15), myxoma resistance protein 1 (Mx1), and protein kinase R (PKR). Thus, our experimental results provide important information about the antiviral functions and mechanism of poIFN-α.

In recent years, the occurrence of a wide variety of drug-resistant diseases has led to an increase in interest in alternate therapies. Peptide-based drugs as an alternate therapy hold researchers' attention in various therapeutic fields such as neurology, dermatology, oncology, metabolic diseases, etc. Previously, they had been overlooked by pharmaceutical companies due to certain limitations such as proteolytic degradation, poor membrane permeability, low oral bioavailability, shorter half-life, and poor target specificity. Over the last two decades, these limitations have been countered by introducing various modification strategies such as backbone and side-chain modifications, amino acid substitution, etc. which improve their functionality. This has led to a substantial interest of researchers and pharmaceutical companies, moving the next generation of these therapeutics from fundamental research to the market. Various chemical and computational approaches are aiding the production of more stable and long-lasting peptides guiding the formulation of novel and advanced therapeutic agents. However, there is not a single article that talks about various peptide design approaches i.e., in-silico and in-vitro along with their applications and strategies to improve their efficacy. In this review, we try to bring different aspects of peptide-based therapeutics under one article with a clear focus to cover the missing links in the literature. This review draws emphasis on various in-silico approaches and modification-based peptide design strategies. It also highlights the recent progress made in peptide delivery methods important for their enhanced clinical efficacy. The article would provide a bird's-eye view to researchers aiming to develop peptides with therapeutic applications.

A vaccine is defined as a biologic preparation that trains the immune system, boosts immunity, and protects against a deadly microbial infection. They have been used for centuries to combat a variety of contagious illnesses by means of subsiding the disease burden as well as eradicating the disease. Since infectious disease pandemics are a recurring global threat, vaccination has emerged as one of the most promising tools to save millions of lives and reduce infection rates. The World Health Organization reports that immunization protects three million individuals annually. Currently, multi-epitope-based peptide vaccines are a unique concept in vaccine formulation. Epitope-based peptide vaccines utilize small fragments of proteins or peptides (parts of the pathogen), called epitopes, that trigger an adequate immune response against a particular pathogen. However, conventional vaccine designing and development techniques are too cumbersome, expensive, and time-consuming. With the recent advancement in bioinformatics, immunoinformatics, and vaccinomics discipline, vaccine science has entered a new era accompanying a modern, impressive, and more realistic paradigm in designing and developing next-generation strong immunogens. designing and developing a safe and novel vaccine construct involves knowledge of reverse vaccinology, various vaccine databases, and high throughput techniques. The computational tools and techniques directly associated with vaccine research are extremely effective, economical, precise, robust, and safe for human use. Many vaccine candidates have entered clinical trials instantly and are available prior to schedule. In light of this, the present article provides researchers with up-to-date information on various approaches, protocols, and databases regarding the computational designing and development of potent multi-epitope-based peptide vaccines that can assist researchers in tailoring vaccines more rapidly and cost-effectively.

Biologically active plant peptides, consisting of secondary metabolites, are compounds (amino acids) utilized by plants in their defense arsenal. Enzymatic processes and metabolic pathways secrete these plant peptides. They are also known for their medicinal value and have been incorporated in therapeutics of major human diseases. Nevertheless, its limitations (low bioavailability, high cytotoxicity, poor absorption, low abundance, improper metabolism, etc.) have demanded a need to explore further and discover other new plant compounds that overcome these limitations. Keeping this in mind, therapeutic plant proteins can be excellent remedial substitutes for bodily affliction. A multitude of these peptides demonstrates anti-carcinogenic, anti-microbial, anti-HIV, and neuro-regulating properties. This article's main aim is to list out and report the status of various therapeutic plant peptides and their prospective status as peptide-based drugs for multiple diseases (infectious and non-infectious). The feasibility of these compounds in the imminent future has also been discussed.

The white spot disease causes significant damage to global aquaculture production. A prominent vaccine, eliciting the immunogenicity of freshwater fishes against yet to be developed. Thus, an Immunoinformatic drive was implemented to find out the potential epitopes from the surface immobilization antigens. B-cell derived T-cell epitopes are promiscuous elements for new generation peptide-based vaccine designing. A total of eight common B and T-cell epitopes had filtered out with no overlapping manner. Subsequently, the common epitopes are linked up with EAAAKEAAAKEAAAK linker peptides, we also added L7/L12 ribosomal protein adjuvant at the N- terminal side of peptide sequence for eliciting the immune response in a better way. The secondary and tertiary structural properties of the modeled 3D protein revealed that the protein had all the properties required for a protective immunogen. Afterward, three globally used validation server: PROCKECK, ProSA and ERRAT were used to justify the proper coordinate. NMR, Crystallographic range and error plot calculation for vaccine model also been done respectively. This was followed by molecular docking, MD simulation, NMA analysis, cloning and vaccine dose-based immune response simulation to evaluate the immunogenic potency of the vaccine construct. The immune simulation in response to multi-epitopes show antibody generation and elevated levels of cell-mediated immunity during repeated exposure of the vaccine. The favourable results of the analysis significantly specify that the vaccine construct is really a powerful vaccine candidate and ready to proceed to the next steps of experimental validation and efficacy studies.

Cryptosporidiosis is the leading protozoan-induced cause of diarrheal illness in children, and it has been linked to childhood mortality, malnutrition, cognitive development, with retardation of growth. , the anthroponotically transmitted species within the genus, contributes significantly to the global burden of infection, accounting for the majority of clinical cases in numerous nations, as well as its emergence in the last decade is largely due to detections obtained through noteworthy epidemiologic research. Nevertheless, there is no vaccine available, and the only licensed medication, nitazoxanide, has been demonstrated to have efficacy limitations in a number of patient groups recognized to be at high risk of complications. Therefore, current study delineates the computational vaccine design for the notable pathogen for enteric diarrhea. Firstly, a comprehensive literature search was conducted to identify six proteins based on their toxigenicity, allergenicity, antigenicity, and prediction of transmembrane helices to make up a multi-epitope-based subunit vaccine. Following that, antigenic non-toxic HTL epitope, CTL epitope with B cell epitope were predicted from the selected proteins and construct a vaccine candidate with adding an adjuvant and some linkers with immunologically superior epitopes. Afterwards, the constructed vaccine candidates and TLR2 receptor were put into the ClusPro server for molecular dynamic simulation to know the binding stability of the vaccine-TLR2 complex. Following that, strain K12 was used as a cloning host for the chosen vaccine construct via the JCat server. As a result of the findings, it was resolute that the proposed chimeric peptide vaccine could improve the immune response to .

In the design and development of therapeutic agents, macromolecules with restricted structures have stronger competitive edges than linear biological entities since cyclization can overcome the limitations of linear structures. The common issues of linear peptides include susceptibility to degradation of the peptidase enzyme, off-target effects, and necessity of routine dosing, leading to instability and ineffectiveness. The unique conformational constraint of cyclic peptides provides a larger surface area to interact with the target at the same time, improving the membrane permeability and in vivo stability compared to their linear counterparts. Currently, cyclic peptides have been reported to possess various activities, such as antifungal, antiviral and antimicrobial activities. To date, there is emerging interest in cyclic peptide therapeutics, and increasing numbers of clinically approved cyclic peptide drugs are available on the market. In this review, the medical significance of cyclic peptides in the defence against viral infections will be highlighted. Except for chikungunya virus, which lacks specific antiviral treatment, all the viral diseases targeted in this review are those with effective treatments yet with certain limitations to date. Thus, strategies and approaches to optimise the antiviral effect of cyclic peptides will be discussed along with their respective outcomes. Apart from isolated naturally occurring cyclic peptides, chemically synthesized or modified cyclic peptides with antiviral activities targeting coronavirus, herpes simplex viruses, human immunodeficiency virus, Ebola virus, influenza virus, dengue virus, five main hepatitis viruses, termed as type A, B, C, D and E and chikungunya virus will be reviewed herein.

Crimean-Congo hemorrhagic fever (CCHF) is a viral disease caused by the Crimean-Congo hemorrhagic fever virus (CCHFV) of the Nairovirus genus. CCHF has occurred endemically in several regions of Africa, Southern Europe, and Central and Southeast Asia, with a case fatality rate of 5 to 80%. The World health organization enlisted CCHF as one of the top prioritized diseases for research and development in emergency contexts that making it a public health concern as no effective vaccine is available till date. Therefore, the present study aims to develop an effective multi-epitope subunit vaccine using immunoinformatics and reverse vaccinology approach against this virus. The B-cell and T-cell epitopes were predicted from structural and non-structural proteins, and filtered by immunogenicity, allergenicity, toxicity, conservancy, and cross-reactivity. The computational analysis revealed that the epitopes could induce an adequate immune response and had strong associations with their respective human leukocyte antigen (HLA) alleles with 98.94% of total world population coverage. Finally, the vaccine with 427 amino acids was constructed by connecting 8 cytotoxic T-lymphocytes, 4 helper T-lymphocytes, and 10 B-cell epitopes with appropriate linkers and β-defensin as an adjuvant. The antigenicity, allergenicity, solubility, and physiochemical properties of the vaccine were evaluated, followed by structural modelling, refinement, and validation. In addition, molecular docking and molecular dynamic simulations revealed a robust binding affinity and stability of the vaccine-immune receptor complex. Moreover, the codons were optimized for its higher expression in () K12 strain followed by in silico cloning. The proposed subunit vaccine developed in this study could be a potential candidate against CCHFV. However, further experimental validation is required to ensure the immunogenicity and safety profile of the proposed vaccine for combating and eradicating CCHFV.

In spite of existing cases of severe viral infections with a high mortality rate, there are not enough antiviral drugs and vaccines available for the prevention and treatment of such diseases. In addition, the increasing reports of the emergence of viral epidemics highlight, the need for novel molecules with antiviral potential. Antimicrobial peptides (AMPs) with antiviral activity or antiviral peptides (AVPs) have turned into a research hotspot and already show tremendous potential to become pharmaceutically available antiviral medicines. AMPs, a diverse group of bioactive peptides act as a part of our first line of defense against pathogen inactivation. Although most of the currently reported AMPs are either antibacterial or antifungal peptides, the number of antiviral peptides is gradually increasing. Some of the AMPs that are shown as effective antivirals have been deployed against viruses such as influenza A virus, severe acute respiratory syndrome coronavirus (SARS-CoV), HIV, HSV, West Nile Virus (WNV), and other viruses. This review offers an overview of AVPs that have been approved within the past few years and will set out a few of the most essential patents and their usage within the context mentioned above during 2000-2020. Moreover, the present study will explain some of the progress in antiviral drugs based on peptides and peptide-related antivirals.

Invasive candidiasis is an emerging fungal infection and a leading cause of morbidity in health care facilities. Despite advances in antifungal therapy, increased antifungal drug resistance in has enhanced patient fatality. The most common method for diagnosing is blood culture, which has low sensitivity. Therefore, there is an urgent need to establish a valid diagnostic method. Our study aimed to use the bioinformatics approach to design a diagnostic kit for detecting with high sensitivity and specificity. Eight antigenic proteins of (HYR1, HWP1, ECE1, ALS, EAP1, SAP1, BGL2, and MET6) were selected. Next, a construct containing different immunodominant B-cell epitopes was derived from the antigens and connected using a suitable linker. Different properties of the final construct, such as physicochemical properties, were evaluated. Moreover, the designed construct underwent 3D modeling, reverse translation, and codon optimization. The results confirmed that the designed construct could identify with high sensitivity and specificity in serum samples of patients with invasive candidiasis. However, experimental studies are needed for final confirmation.

GHRH is produced in the hypothalamus and affects various tissues beyond the pituitary, including the lungs. GHRH antagonists exert anti-inflammatory properties in several experimental models of disease, but their role inprotecting the endothelial barrier during inflammation is less understood. This study investigates the effects ofGHRHAnt on LPS-induced endothelial dysfunction.