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Human cytomegalovirus (HCMV) is a widespread virus that can cause serious and irreversible neurological damage in newborns and even death in children who do not have the access to much-needed medications. While some vaccines and drugs are found to be effective against HCMV, their extended use has given rise to dose-limiting toxicities and the development of drug-resistant mutants among patients. Despite half a century’s worth of research, the lack of a licensed HCMV vaccine heightens the need to develop newer antiviral therapies and vaccine candidates with improved effectiveness and reduced side effects. In this study, the immunoinformatics approach was utilized to design a potential polyvalent epitope-based vaccine effective against the four virulent strains of HCMV. The vaccine was constructed using seven CD8+ cytotoxic T lymphocytes epitopes, nine CD4+ helper T lymphocyte epitopes, and twelve linear B-cell lymphocyte epitopes that were predicted to be antigenic, non-allergenic, non-toxic, fully conserved, and non-human homologous. Subsequently, molecular docking study, protein-protein interaction analysis, molecular dynamics simulation (including the root mean square fluctuation (RMSF) and root mean square deviation (RMSD)), and immune simulation study rendered promising results assuring the vaccine to be stable, safe, and effective. Finally, in silico cloning was conducted to develop an efficient mass production strategy of the vaccine. However, further in vitro and in vivo research studies on the proposed vaccine are required to confirm its safety and efficacy. Communicated by Ramaswamy H. Sarma

Coronaviruses have marked their significant emergence since the twenty-first century with the outbreaks of three out of the seven existing human coronaviruses, including the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2003, Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in 2019. These viruses have not only acquired large-scale transmission during their specified outbreak period, but cases of MERS-CoV still remain active, although there is only limited transmission. While, on the other hand, SARS-CoV-2 continues to remain a rising threat to global public health. The recent novel coronavirus, SARS-CoV-2, responsible for the ongoing coronavirus disease 2019 (COVID-19), emerged during December 2019 in Wuhan, China, and has repeatedly raised questions about its characteristic variability. Despite belonging to the same family, SARS-CoV-2 has proven to be quite difficult to control and contain in terms of transmissibility, leading to around 19.8 million reported cases and more than 730,000 deaths of individuals worldwide. Here, we discuss how SARS-CoV-2 differs from its two other related human coronaviruses in terms of genome composition, site of infection, and transmissibility, among several other notable aspects-all indicating to the possibility that it is these variations in addition to other unknowns that are contributing to this virus' differing deadly pattern.

Human Respiratory Syncytial Virus (RSV) is one of the most prominent causes of lower respiratory tract infections (LRTI), contributory to infecting people from all age groups - a majority of which comprises infants and children. The implicated severe RSV infections lead to numerous deaths of multitudes of the overall population, predominantly the children, every year. Consequently, despite several distinctive efforts to develop a vaccine against the RSV as a potential countermeasure, there is no approved or licensed vaccine available yet, to control the RSV infection effectively. Therefore, through the utilization of immunoinformatics tools, a computational approach was taken in this study, to design and construct a multi-epitope polyvalent vaccine against the RSV-A and RSV-B strains of the virus. Potential predictions of the T-cell and B-cell epitopes were followed by extensive tests of antigenicity, allergenicity, toxicity, conservancy, homology to human proteome, transmembrane topology, and cytokine-inducing ability. The most promising epitopes (i.e. 13 CTL epitopes, 9 HTL epitopes, and 10 LBL epitopes) exhibiting full conservancy were then selected for designing the peptide fusion with appropriate linkers, having hBD-3 as the adjuvant. The peptide vaccine was modeled, refined, and validated to further improve the structural attributes. Following this, molecular docking analysis with specific TLRs was carried out which revealed excellent interactions and global binding energies. Additionally, molecular dynamics (MD) simulation was conducted which ensured the stability of the interactions between vaccine and TLR. Furthermore, mechanistic approaches to imitate and predict the potential immune response generated by the administration of vaccines were determined through immune simulations. Owing to an overall evaluation, in silico cloning was carried out in efforts to generate recombinant pETite plasmid vectors for subsequent mass production of the vaccine peptide, incorporated within E.coli. However, more in vitro and in vivo experiments can further validate its efficacy against RSV infections.

The gastrointestinal tract of every healthy human consists of a unique set of gut microbiota that collectively harbors a diverse and complex community of over 100 trillion microorganisms, including bacteria, viruses, archaea, protozoa and fungi. Gut microbes have a symbiotic relationship with our body. The composition of the microbiota is shaped early in life by gut maturation, which is influenced by several factors. Intestinal bacteria are crucial in maintaining immune and metabolic homeostasis and protecting against pathogens. Dysbiosis of gut microbiota is associated not only with intestinal disorders but also with extraintestinal diseases such as metabolic and neurological disorders. In this review, the authors examine different studies that have revealed the possible hypotheses and links in the development of neurological disorders associated with the gut microbiome.

Alzheimer’s disease (AD) and Parkinson’s disease (PD) are two most prevalent age-related dementias that severely affect a large number of elderly people around the globe. Poor understanding of pathogenesis of these neurological diseases imposes challenge to discover therapeutic measures and effective diagnosis methods. In this study, a network-based approach was utilized to identify potential common molecular signatures and therapeutic agents for AD and PD. Protein-protein interaction analysis revealed NCK1, UBC, CDH1, CDC20, ACTB, PSMA7, PRPF8, RPL7, XRCC6 and HSP90AB1 as the best proteome signatures. Different regulatory transcriptional signatures i.e., YY1, NFKB1, BRCA1, TP53, GATA2, SREBF2, E2F1, FOXC1, RELA and NFIC and post-transcriptional signatures i.e., hsa-mir-186-5p, hsamir-92a-3p, hsa-mir-615-3p, hsa-let-7c-5p, hsa-mir-100-5p, hsa-mir-93-3p, hsa-mir-5681a, hsamir-484, hsa-mir-193b-3p and hsa-mir-16p-5p were identified from other interaction network. Drug-gene interaction study revealed possible therapeutic agents which may reverse the AD and PD condition. The scientific approach of this study should contribute to identify potential biomarkers, drug targets and therapeutic agents against AD and PD which should in turn advance the present efforts of scientists to secure effective diagnosis and therapeutic options. However, furtherin vivoandin vitroexperiments might be required to validate the outcomes of this study.

Purpose: This review highlights the global scenario of dengue outbreaks, dengue pathogenesis, symptoms, immune response, diagnosis methods and preventive measures which facilitates the better understanding of the global expansion and concerns relating to the disease. Recent Findings: A recent study showed that natural killer cells of the infected person become activated soon after the infection which may help in treatment and vaccine development. A research team has also produced synthetically engineered mosquitoes that can prevent the transmission and dissemination of the dengue virus by the activation of an antibody. Furthermore, a mutation in the protein envelope of the dengue virus leads to variation in shapes, developing resistance towards the vaccine. Summary: The mosquito vectors marked their worldwide distribution through an increasing number of reported cases which was further facilitated by the growth in the shipping and commerce industries. The immune system, through activation of the innate and adaptive immune responses, facilitates the recruitment of an array of leukocytes which help neutralize the virus. Apart from the laboratory standard PRNT method, several other dengue detection methods such as ELISA, RT-LAMP and several optical, microfluidic and electrochemical methods have been developed. The existence of the 4 different viral serotypes makes the secondary infection life-threatening and also leads to difficulties in vaccine development. Since Dengvaxia® (CYD-TDV) has its own set of drawbacks and limitations, several companies have been investing for the production of more potential vaccines that are currently in trial.

Purpose: This review features a generalized overview of dengue outbreaks, dengue pathogenesis, symptoms, immune response, diagnosis methods and preventive measures which facilitates the better understanding of the global expansion and concerns relating to the disease. Recent Findings: A recent study showed that natural killer cells of the infected person become activated soon after the infection which may help in treatment and vaccine development. A research team has also produced synthetically engineered mosquitoes that can prevent the transmission and dissemination of the dengue virus by the activation of an antibody. Furthermore, a mutation in the protein envelope of the dengue virus leads to variation in shapes, developing resistance towards the vaccine. Summary: The increasing number of reported cases indicated the worldwide distribution of the mosquito vectors, which was further facilitated by the growth in the shipping and commerce industries. The immune system, through activation of the innate and adaptive immune responses, facilitates the recruitment of an array of leukocytes which help neutralize the virus. However, the 4 different viral serotypes increases the risk of a life-threatening secondary infection due to the varying serotypes. Apart from the laboratory standard PRNT method, several other dengue detection methods such as ELISA, RT-LAMP and several optical, microfluidic and electrochemical methods have been developed. Since Dengvaxia® (CYD-TDV) has its own set of drawbacks and limitations, several companies have been investing for the production of more potential vaccines that are currently in trial.