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Around the world, emergence and re-emergence of Dengue Virus (DENV) are one of the serious public health concerns. The infection of DENV to human population is mainly caused by the bite of an Aedes... more...

Monkeypox is a self-limiting zoonotic viral disease and causes smallpox-like symptoms. The disease has a case fatality ratio of 3–6% and, recently, a multi-country outbreak of the disease has occurred. The currently available vaccines that have provided immunization against monkeypox are classified as live attenuated vaccinia virus-based vaccines, which pose challenges of safety and efficacy in chronic infections. In this study, we have used an immunoinformatics-aided design of a multi-epitope vaccine (MEV) candidate by targeting monkeypox virus (MPXV) glycoproteins and membrane proteins. From these proteins, seven epitopes (two T-helper cell epitopes, four T-cytotoxic cell epitopes and one linear B cell epitopes) were finally selected and predicted as antigenic, non-allergic, interferon-γ activating and non-toxic. These epitopes were linked to adjuvants to design a non-allergic and antigenic candidate MPXV-MEV. Further, molecular docking and molecular dynamics simulations predicted stable interactions between predicted MEV and human receptor TLR5. Finally, the immune-simulation analysis showed that the candidate MPXV-MEV could elicit a human immune response. The results obtained from these in silico experiments are promising but require further validation through additional in vivo experiments. more...

Nipah virus was first appeared in Malaysian 1998, which further found be outburst in neighbor countries i.e. Bangladesh, Singapore, and India. Currently there is no effective drug or vaccine available only supportive care and prevention are way to manage it. Epitope based vaccine could be the best way to cure Nipah virus infection. In this study, the proteome of Nipah virus was retrieve from UniProt database and were subjected to check for allergenicity using Allergen FP v.1.0 tool. NetMHCII 2.3 server screened epitopes from non-allergen proteins and Vaxijen tool was used to identify the most antigenic epitopes binds with MHC class II molecules. Two potent T cell epitopes LLFVFGPNL and KYKIKSNPL were found, which binds with HLA-DRB1*01:01 and HLA-DRB1*07:01 MHC class II alleles. PepstrMod and Swiss-Model server were used to build 3D structure model of epitopes and alleles, respectively. Further identified epitopes were docked with HLA alleles using AutoDock vina tool to confirm binding ability. The epitopes LLFVFGPNL and KYKIKSNPL had binding affinity of − 8.1 kcal/mol and − 5.7 kcal/mol with HLA-DRB1*01:01 and HLA-DRB1*07:01 alleles, respectively. Solidity of predicted epitope—allele docked complex were evaluating by molecular dynamics simulation.HLA distribution analysis was performed for predicted epitopes using the population coverage tool of Immune Epitope Database (IEDB). These predicted epitopes cover maximum number of populations in India as well as worldwide. Therefore, these epitopes could be potent vaccine candidates to counter Nipah virus by testing in wet lab. more...

Background Canine circovirus is a deadly pathogen of dogs and causes vasculitis and hemorrhagic enteritis. It causes lethal gastroenteritis in pigs, fox, and dogs. Canine circovirus genome contains two main (and opposite) transcription units which encode two open reading frames (ORFs), a replicase-associated protein (Rep) and the capsid (Cap) protein. The replicase protein and capsid protein consist of 303 amino acids and 270 amino acids respectively. Several immuno-informatics methods such as epitope screening, molecular docking, and molecular-dynamics simulations were used to craft peptide-based vaccine construct against canine circovirus. Results The vaccine construct was designed by joining the selected epitopes with adjuvants by suitable linker. The cloning and expression of the vaccine construct was also performed using in silico methods. Screening of epitopes was conducted by NetMHC server that uses ANN (Artificial neural networking) algorithm. These methods are fast and cost-effective for screening epitopes that can interact with dog leukocyte antigens (DLA) and initiate an immune response. Overall, 5 epitopes, YQHLPPFRF, YIRAKWINW, ALYRRLTLI, HLQGFVNLK, and GTMNFVARR, were selected and used to design a vaccine construct. The molecular docking and molecular dynamics simulation studies show that these epitopes can bind with DLA molecules with stability. The codon adaptation and in silico cloning studies show that the vaccine can be expressed by Escherichia coli K12 strain. Conclusion The results suggest that the vaccine construct can be useful in preventing the dogs from canine circovirus infections. However, the results need further validation by performing other in vitro and in vivo experiments. more...

Neural necrosis virus (NNV) of family Nodaviridae affect wide range of fish species with viral encephalopathy and retinopathy causing mass mortality up to 100%. Currently there is no effective treatment and depopulation is only suggested recommendation. New avenues and approach are required to control this harmful malady. In this study we developed an epitope-based vaccine (EBV), against NNV using computation approach. We have selected two conserved proteins RNA-dependent RNA polymerase (RdRP) and capsid proteins. Based on more than ~ 1000 epitopes we selected six antigenic epitopes. These were conjugated to adjuvant and linker peptides to generate a full-length vaccine candidate. Biochemical structural properties were analyzed by Phyre2 server. ProtParam, Molprobity. Ramachandran plot results indicate that 98.7% residues are in a favorable region and 93.4% residues in the favored region. The engineered EBV binds to toll like receptor-5 (TLR5) an important elicitor of immune response. Further molecular docking by PatchDock server reveals the atomic contact energy (i.e. - 267.08) for the best docked model of EBV and TLR5 receptor. The molecular simulation results suggest a stable interaction; the RMSD and RMSF values are 1-4 Ǻ and 1-12Ǻ, respectively. Further we have suggested the best possible codon optimized sequence for its cloning and subsequent purification of the protein. Overall, this is a first report to suggest an in-silico method for generation of an EBV candidate against NNV. We surmise that the method and approach suggested could be used as a promising cure for NNVs. more...

Candida auris is a rapidly emerging human pathogenic fungus with a high mortality rate. Recent report suggests that the new clinical isolates are showing resistance to the major classes of antifungal drugs. Due to the emergence of drug resistance, it becomes imperative to seek novel therapies for the treatment of C. auris. The potent vaccine could be one of the promising strategies for recalcitrant and multidrug-resistant pathogens. Using in silico approach we designed a novel multivalent vaccine against C. auris. We have selected the agglutinin-like sequence-3 (Als3) an adhesion protein, involved in virulence. The Als3p protein of C. auris was targeted to predict T cell and B cell epitopes. Epitopes which were found to be non-toxic, non-allergenic, highly conserved, and antigenic and could induce interferon-γ synthesis were selected for vaccine design. The selected epitopes were linked with suitable adjuvants to construct the final vaccine. The vaccine construct was predicted to be stable, soluble, antigenic, non-allergic with desirable physicochemical properties. We also constructed the 3D model of the vaccine and validated it with the Ramachandran plot. The ability of the vaccine construct to interact with Toll-like receptor (TLR) and major histocompatibility complex (MHC) was determined by molecular docking experiments. The binding energy of the vaccine construct with the TLR and MHC were found to be stable as predicted by molecular dynamics simulation. Further, in-silico cloning analysis showed that the vaccine construct can be successfully cloned and expressed in E. coli. Based on the results, we surmise that our candidate vaccine can be used as an alternative therapy for the treatment of C. auris. However, the efficacy and the safety of the vaccine model need to be determined by performing in vivo studies. more...

Zika fever is a disease caused by Zika virus which is a mosquito-borne flavivirus and infection is through the bite of mosquito from the Aedes genus. Other mode of transmission of Zika fever is blood transfusion, which is thoroughly investigated. Prominent symptoms of Zika virus fever are mild fever, skin rash, conjunctivitis, muscle and joint pain, malaise or headache. These symptoms normally last for 2–7 days. There is currently no effective and easily affordable vaccine available against Zika virus. Keeping the current status in mind we have devised our objectives to design a peptide-based vaccine against Zika Virus using in-silico approach. The NS3 and NS5 proteins of Zika virus are well known of having important role in replication of the virus that is why we have targeted these proteins for epitope prediction. Prediction and screening of epitopes was performed using IEDB tool. We have also checked the efficacy of these screened epitopes with the help of IC50 value and docking score. “VEMGEAAAI” was found to be the high affinity binding epitope for MHC Class I and MHC Class II molecule. These findings conclude that the predicted epitope could well be used as a potential vaccine candidate for formulations of vaccines against Zika virus. more...

Hepatitis C is widely spread and induces life threatening situations. Researchers from various fields have developed vaccine, but they are not that effective because of the variation in genotype of Hepatitis virus and also not much affordable. In-silico approach is of greater importance in designing and testing the model vaccine. In this study, investigation has been done for the available Bioinformatics tools and methodologies used in HCV research. Different types of tools and databases commonly used by researchers were reviewed to get an overall picture of bioinformatics techniques, computational biology tools and databases used in Hepatitis C Virus research. Exclusive study has also done to figure out different statistical methods used by different research groups. This paper will provide an up-to-date picture of computation approaches used for exploring Hepatitis C treatment. more...

Human Cytomegalovirus (HCMV) is one of the most common causes of congenital infections globally. They infect the fetus and cause severe birth defects such as hearing loss, complications in the eyes, epilepsy, autism, and various other neurological disorders. They are also the leading cause of death in patients with compromised immunity. Due to the prevalence and severity of the virus, the United States National Academy of Medicine has announced the development of the HCMV vaccine as a matter of high priority for public health. Hence, this study is focused on designing a novel potent multi-epitope HCMV vaccine. The envelope glycoproteins B, H, L and M of HCMV were targeted to predict T cell (both Helper and Cytotoxic) epitopes that were non-toxic, highly antigenic, and non-allergenic and could induce interferon-γ production. Further, the selected epitopes were subjected to molecular docking and population coverage analysis. Eventually, using the two best epitopes and adjuvants like RS09, flagellin protein and PADRE sequence a 283 amino acid long vaccine was designed. The vaccine is antigenic, non-allergenic, stable, and soluble. The 3D model of the vaccine was developed and validated using the Ramachandran plot. Docking with Toll-like receptor 5 (TLR5) molecule and molecular dynamics simulation confirmed the stability of the vaccine. In silico cloning simulation using pET28a (+) vector showed that the vaccine can be successfully cloned and expressed in E. coli K12 strain. However, the efficacy and the safety of the vaccine need to be further validated by in vivo studies. more...

Introduction of vaccines has been one of the most vital offering of immunology to public health till date. Present influenza vaccines basically induce antibody responses to the hemagglutinin protein of the viral strains selected for the vaccine. Peptide based vaccine are formulated by combining conserved B and T cell epitopes. Recent progress has been made in the discovery of vaccines based on use of peptides. This study evaluates the capacity of four epitopes to induce specific immune response and protect human against viral infection. Predicted YEELREQLSSVSS epitope could further be taken by scientist for development of vaccine against swine flu. more...

Hepatitis C is a severe disease caused by Hepatitis C virus which leads to human fatality and affected 180 million people across the globe. Its chronic infection leads to liver damage and malignant hepatoma. Till now there is no vaccine in the market for this virus. The objective of the study was to predict the best epitope using Bioinformatics tools for designing a vaccine against HCV. Here T-cell epitope was considered since it can recognize only antigen that processes to generate peptide by antigen presenting cell. For selecting the best T cell epitope, the binding energy with the MHC molecule must be high, must have a protease cleavage site, conserved site, motif, good binder with hydrophobic binding pocket and half-life of dissociation must be high. By considering above criteria suitable bioinformatics tools were used to predict the epitopes from NS3, NS5A and NS5B of 3a and 3b genotype. A total of 600 epitopes from different tools for each protein were predicted and from there only 11 efficient epitopes was virtually screened out using protein-protein interaction between MHC-I and MHC-II molecules and their energy. IMYAPTIWV peptide of NS5A protein was found to be the best epitope. The selected epitope for T-cell can further be used for future work in a wet laboratory for the development of vaccine against HCV. more...

Hepatitis C virus (HCV) being an infectious disease is prevalent in most parts of the world. Till date, no vaccine is being developed in the market for HCV. This paper focuses mainly on developing a peptide-based vaccine against HCV. The purpose for this study is taken to determine the suitable epitope with the help of Bioinformatics tools developed for designing a vaccine against infectious diseases such as HCV. In present work, T-cell epitope is taken into consideration, as it recognises the antigen that helps to generate peptide with the help of antigen presenting cell. With respect to T-cell epitope selection, high binding energy must be required for binding major histocompatibility complex molecule. Moreover, T-cell epitope were considered on the basis of conserved site, protease cleavage site, motif, as well as an excellent hydrophobic binding pocket with a high half-life of dissociation. In consideration to the mentioned criteria, the required bioinformatics tools are used which are designed to predict the epitopes from different envelope and non-structural proteins of HCV virus. On an average, 1,000 epitopes from various databases and tools were extracted, from which 11 adept epitopes were withdrawn virtually with a base of binding energy using MHC I and II molecule protein interaction. The best epitope predicted during study was IMYAPTIWV peptide of NS5A protein. The T-cell predicted epitope can be further used for later chore in vaccine discovery for HCV. more...