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      Immunoinformatic-Based Multi-Epitope Vaccine Design for Co-Infection of Mycobacterium tuberculosis and SARS-CoV-2

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      Journal of Personalized Medicine
      MDPI AG

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          Abstract

          (1) Background: Many co-infections of Mycobacterium tuberculosis (MTB) and severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) have emerged since the occurrence of the SARS-CoV-2 pandemic. This study aims to design an effective preventive multi-epitope vaccine against the co-infection of MTB and SARS-CoV-2. (2) Methods: The three selected proteins (spike protein, diacylglycerol acyltransferase, and low molecular weight T-cell antigen TB8.4) were predicted using bioinformatics, and 16 epitopes with the highest ranks (10 helper T lymphocyte epitopes, 2 CD8+ T lymphocytes epitopes, and 4 B-cell epitopes) were selected and assembled into the candidate vaccine referred to as S7D5L4. The toxicity, sensitization, stability, solubility, antigenicity, and immunogenicity of the S7D5L4 vaccine were evaluated using bioinformatics tools. Subsequently, toll-like receptor 4 docking simulation and discontinuous B-cell epitope prediction were performed. Immune simulation and codon optimization were carried out using immunoinformatics and molecular biology tools. (3) Results: The S7D5L4 vaccine showed good physical properties, such as solubility, stability, non-sensitization, and non-toxicity. This vaccine had excellent antigenicity and immunogenicity and could successfully simulate immune responses in silico. Furthermore, the normal mode analysis of the S7D5L4 vaccine and toll-like receptor 4 docking simulation demonstrated that the vaccine had docking potential and a stable reaction. (4) Conclusions: The S7D5L4 vaccine designed to fight against the co-infection of MTB and SARS-CoV-2 may be safe and effective. The protective efficacy of this promising vaccine should be further verified using in vitro and in vivo experiments.

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          Most cited references69

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          A Novel Coronavirus from Patients with Pneumonia in China, 2019

          Summary In December 2019, a cluster of patients with pneumonia of unknown cause was linked to a seafood wholesale market in Wuhan, China. A previously unknown betacoronavirus was discovered through the use of unbiased sequencing in samples from patients with pneumonia. Human airway epithelial cells were used to isolate a novel coronavirus, named 2019-nCoV, which formed a clade within the subgenus sarbecovirus, Orthocoronavirinae subfamily. Different from both MERS-CoV and SARS-CoV, 2019-nCoV is the seventh member of the family of coronaviruses that infect humans. Enhanced surveillance and further investigation are ongoing. (Funded by the National Key Research and Development Program of China and the National Major Project for Control and Prevention of Infectious Disease in China.)
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            SWISS-MODEL: homology modelling of protein structures and complexes

            Abstract Homology modelling has matured into an important technique in structural biology, significantly contributing to narrowing the gap between known protein sequences and experimentally determined structures. Fully automated workflows and servers simplify and streamline the homology modelling process, also allowing users without a specific computational expertise to generate reliable protein models and have easy access to modelling results, their visualization and interpretation. Here, we present an update to the SWISS-MODEL server, which pioneered the field of automated modelling 25 years ago and been continuously further developed. Recently, its functionality has been extended to the modelling of homo- and heteromeric complexes. Starting from the amino acid sequences of the interacting proteins, both the stoichiometry and the overall structure of the complex are inferred by homology modelling. Other major improvements include the implementation of a new modelling engine, ProMod3 and the introduction a new local model quality estimation method, QMEANDisCo. SWISS-MODEL is freely available at https://swissmodel.expasy.org.
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              The role of pattern-recognition receptors in innate immunity: update on Toll-like receptors.

              The discovery of Toll-like receptors (TLRs) as components that recognize conserved structures in pathogens has greatly advanced understanding of how the body senses pathogen invasion, triggers innate immune responses and primes antigen-specific adaptive immunity. Although TLRs are critical for host defense, it has become apparent that loss of negative regulation of TLR signaling, as well as recognition of self molecules by TLRs, are strongly associated with the pathogenesis of inflammatory and autoimmune diseases. Furthermore, it is now clear that the interaction between TLRs and recently identified cytosolic innate immune sensors is crucial for mounting effective immune responses. Here we describe the recent advances that have been made by research into the role of TLR biology in host defense and disease.
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                Author and article information

                Contributors
                Journal
                JPMOB3
                Journal of Personalized Medicine
                JPM
                MDPI AG
                2075-4426
                January 2023
                January 05 2023
                : 13
                : 1
                : 116
                Article
                10.3390/jpm13010116
                4f6d443f-dbf5-4b22-88ce-fbde034edeb5
                © 2023

                https://creativecommons.org/licenses/by/4.0/

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