The emerging monkeypox virus (MPXV) is a zoonotic orthopoxvirus that causes infections in humans similar to smallpox. Since May 2022, cases of monkeypox (MPX) have been increasingly reported by the World Health Organization (WHO) worldwide. Currently, there are no clinically validated treatments for MPX infections. In this study, an immunoinformatics approach was used to identify potential vaccine targets against MPXV. A total of 190 MPXV-2022 proteins were retrieved from the ViPR database and subjected to various analyses including antigenicity, allergenicity, toxicity, solubility, IFN-γ, and virulence. Three outer membrane and extracellular proteins were selected based on their respective parameters to predict B-cell and T-cell epitopes. The epitopes are conserved among different strains of MPXV and the population coverage is 100% worldwide, which will provide broader protection against various strains of the virus globally. Nine overlapping MHC-I, MHC-II, and B-cell epitopes were selected to design multi-epitope vaccine constructs linked with suitable linkers in combination with different adjuvants to enhance the immune responses of the vaccine constructs. Molecular modeling and structural validation ensured high-quality 3D structures of vaccine constructs. Based on various immunological and physiochemical properties and docking scores, MPXV-V2 was selected for further investigation. In silico cloning revealed a high level of gene expression for the MPXV-V2 vaccine within the bacterial expression system. Immune and MD simulations confirmed the molecular stability of the MPXV-V2 construct, with high immune responses within the host cell. These results may aid in the development of experimental vaccines against MPXV with increased potency and improved safety.
Human papilloma virus (HPV) is a serious threat to human life globally with over 100 genotypes including cancer causing high risk HpVs. Study on protein interaction maps of pathogens with their host is a recent trend in 'omics' era and has been practiced by researchers to find novel drug targets. in current study, we construct an integrated protein interaction map of HpV with its host human in Cytoscape and analyze it further by using various bioinformatics tools. We found out 2988 interactions between 12 HPV and 2061 human proteins among which we identified MYLK, CDK7, CDK1, CDK2, JAK1 and 6 other human proteins associated with multiple viral oncoproteins. The functional enrichment analysis of these top-notch key genes is performed using KEGG pathway and Gene Ontology analysis, which reveals that the gene set is enriched in cell cycle a crucial cellular process, and the second most important pathway in which the gene set is involved is viral carcinogenesis. Among the viral proteins, E7 has the highest number of associations in the network followed by E6, E2 and E5. We found out a group of genes which is not targeted by the existing drugs available for HpV infections. it can be concluded that the molecules found in this study could be potential targets and could be used by scientists in their drug design studies. Human papilloma virus (HPV) is associated with approximately 5% of all human cancers affecting 0.6 million people worldwide with cervical, anal, oropharyngeal, penile and vulvovaginal cancers 1-3. Among these cancers, cervical cancer ranks 4th in affecting women worldwide 4 while in developing countries it ranks second 5. According to World Health Organization (WHO) current factsheets, there are more than 100 genotypes of HPV, out of which 14 strains are high-risk. The most talked about high-risk HPV strains are HPV 6, 11, 16, 18, 31, 33, 35, 45, 52 and 58 with type 16 and 18 responsible for 70% of cervical cancer cases 6-8. HPV is a serious threat to human life and it is causing 250,000 deaths annually, among which 85% of cases are occurring in low and middle-income countries 9. HPV is a small ~8 kb in size, non-enveloped circular dsDNA virus 5,10. The HPV genome encodes 8 proteins among which 2 are structural viral capsid proteins (L1 and L2) while 6 are non-structural viral proteins (E1, E2, E4, E5, E6, E7) 10,11. Besides these 8 proteins, there are a few other macromolecules found in literature which are actually the transcripts made by the fusion of two existing HPV proteins. E8∧E2, a transcript, is created by the fusion of E8 with carboxy terminal of E2 12 , and E1∧E4 is generated by the fusion of E1 to the Open Reading Frame (ORF) of E4 13. Protein interaction network provides a plethora of information when it comes to virus-host relationship because viruses entirely depend upon the host factors for their survival 14,15. Viruses tend to regulate host biological processes by manipulating its cell proteome. Researchers have been using network biology for designing novel antiviral drug therapies 16. ...
Clinical epidemiological studies have reported that viral infections cause autoimmune pathology in humans. Host-pathogen protein sequences and structure-based molecular mimicry cause autoreactive T cells to cross-activate. The aim of the current study was to implement immunoinformatics approaches to infer sequence- and structure-based molecular mimicry between viral and human proteomic datasets. The protein sequences of all the so far known human-infecting viruses were obtained from the VIPR database, and complete human proteome data were retrieved from the NCBI repository. Based on a predefined, stringent threshold of comparative sequence analyses, 24 viral proteins were identified with significant sequence similarity to human proteins. PathDIP identified the enrichment of these homologous proteins in nine metabolic pathways with a p-value < 0.0001. Several viral and human mimic epitopes from these homologous proteins were predicted as strong binders of human HLA alleles, with IC50 < 50 nM. Downstream molecular docking analyses identified that lead virus-human homologous epitopes feasibly interact with HLA and TLR4 types of immune receptors. The vast majority of these top-hit homolog epitopic peptides belong to the herpes simplex and poxvirus families. These lead epitope biological sequences and 3D structural-based molecular mimicry may be promising for interpreting herpes simplex virus and poxvirus infection-mediated autoimmune disorders in humans.
The decreasing cost of genome-level DNA sequencing due to technological advancement in the form of nextgeneration sequencing allowed to understand the ecological diversity and dynamic functionality of microbial communities with increase resolution. Nowadays, these fast genome sequencing along with advance bioinformatics resources transformed the secondary
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