Identification of potential vaccine targets for elicitation of host immune cells against SARS-CoV-2 by reverse vaccinology approach.

The COVID-19 pandemic has emerged as a critical global health crisis, demanding urgent and effective strategies for containment. While some knowledge exists about epitope sequences recognized by human immune cells and their activation of CD8+ T cells within the HLA context, comprehensive information remains limited. This study employs reverse vaccinology to explore antigenic HLA-restricted T-cell epitopes capable of eliciting durable immunity. Screening reveals 187 consensus epitopes, with 23 offering broad population coverage worldwide, spanning over 5000 HLA alleles. Sequence alignment analysis highlights the genetic distinctiveness of these peptides from Homo sapiens and their intermediate to high TAP binding efficiency. Notably, these epitopes share 100 % sequence identity across strains from nine countries, indicating potential for a uniform protective immune response among diverse ethnic populations. Docking simulations further confirm their binding capacity with the HLA allele, validating them as promising targets for SARS-CoV-2 immune recognition. The anticipated epitopes are connected with suitable linkers and adjuvant, and then assessed for its translational efficacy within a bacterial expression vector through computational cloning. Through docking, it is observed that the chimeric vaccine construct forms lasting hydrogen bonds with Toll-like receptor (TLR4), while immune simulation illustrates an increased cytotoxic response aimed at CD8+ T cells. This comprehensive computational analysis suggests the chimeric vaccine construct's potential to provoke a robust immune response against SARS-CoV-2. By delineating these antigenic fragments, our study offers valuable insights into effective vaccine and immunotherapy development against COVID-19, contributing significantly to global efforts in combating this infectious threat.

Are Proton Pump Inhibitors Contributing in Emerging New Hypertensive Population?

Balancing the therapeutic advantages of a medicine with its possible risks and side effects is an important part of medical practice and drug regulation. When a drug is designed to treat a particular disease or medical condition ends up causing additional risks or side effects that lead to the development of other serious health problems, it can have detrimental consequences for patients. This article explores the correlation between persistent proton pump inhibitor (PPI) use and hypertension, a common cardiovascular ailment. While PPIs are beneficial in treating various gastrointestinal problems, their availability without a prescription has resulted in self-medication and long-term use without medical monitoring. Recent findings have revealed a link between long-term PPI usage and increased cardiovascular risks, particularly hypertension. This study investigates the intricate mechanisms underlying PPI's effects, focusing on potential pathways contributing to hypertension, such as endothelial dysfunction, disruption of nitric oxide bioavailability, vitamin B deficiency, hypocalcemia, and hypomagnesemia. The discussion explains how long-term PPI use can disrupt normal endothelial function, vascular control, and mineral balance, eventually leading to hypertension. The article emphasizes the significance of using PPIs with caution and ongoing research to better understand the implications of these medications on cardiovascular health.

Novel Drug Delivery Systems as an Emerging Platform for Stomach Cancer Therapy.

Cancer has long been regarded as one of the world's most fatal diseases, claiming the lives of countless individuals each year. Stomach cancer is a prevalent cancer that has recently reached a high number of fatalities. It continues to be one of the most fatal cancer forms, requiring immediate attention due to its low overall survival rate. Early detection and appropriate therapy are, perhaps, of the most difficult challenges in the fight against stomach cancer. We focused on positive tactics for stomach cancer therapy in this paper, and we went over the most current advancements and progressions of nanotechnology-based systems in modern drug delivery and therapies in great detail. Recent therapeutic tactics used in nanotechnology-based delivery of drugs aim to improve cellular absorption, pharmacokinetics, and anticancer drug efficacy, allowing for more precise targeting of specific agents for effective stomach cancer treatment. The current review also provides information on ongoing research aimed at improving the curative effectiveness of existing anti-stomach cancer medicines. All these crucial matters discussed under one overarching title will be extremely useful to readers who are working on developing multi-functional nano-constructs for improved diagnosis and treatment of stomach cancer.

Mining the Proteome of Leishmania donovani for the Development of Novel MHC Class I Restricted Epitope for the Control of Visceral Leishmaniasis.

Although, the precise host defence mechanism(s) is not completely understood, T cell-mediated immune responses is believed to play a pivotal role in controlling parasite infection. Here we target the stage dependent over expressed gene. Here, the consensus based computational approach was adopted for the screening of potential major histocompatibility complex class I restricted epitopes. Based on the computational analysis and previously published report, a set 19 antigenic proteins derived from Leishmania donovani were screened for further characterization as vaccine candidates. A total of 49 epitopes were predicted, which revealed a comprehensive binding affinity to the 40 different MHC class I supertypes. Based on the population coverage and HLA cross presentation, nine highly promiscuous epitopes such as LTYDDVWTV (P1), FLFPQRTAL(P2), FLFSNGAVV (P3), YIYNFGIRV (P4), YMTAAFAAL (P5), KLLRPFAPL (P6), FMLGWIVTI (P7), SLFERNKRV (P8), and SVWNRIFTL (P9) which have either a high or an intermediate TAP binding affinity were selected for further analysis. Theoretical population coverage analysis of polytope vaccine (P1-P9) revealed more than 92% population. Stimulation with the cocktail of peptide revealed a proliferative CD8+ T cell response and increased IFN-γ production. An upregulated NF-κB activity is thought to be play a pivotal role in T cell proliferation against the selected peptide. The Th1-type cytokine profile (presence of IFN-γ and absence of IL-10) suggests the potentiality of the cocktail of epitope as a subunit vaccine against leishmaniasis. However, the efficiency of these epitopes to trigger other Th1 cytokines and chemokines in a humanized mice model could explore its plausibility as a vaccine candidate. J. Cell. Biochem. 119: 378-391, 2018. © 2017 Wiley Periodicals, Inc.

Tuberculosis: current treatment, diagnostics, and newer antitubercular agents in clinical trials.

Tuberculosis (TB), a dreadful disease is one of the most important health problems worldwide, and is responsible for approximately 1.3 million death tolls in 2012. DOTS is the currently used drug therapy in TB and the long term drug regimens and patients' poor compliance lead to emergence of multidrug resistant (MDR) and extensively drug resistant (XDR) TB, which invigorates the research efforts to address the urgent need for the quick diagnosis and for newer antitubercular agents and vaccines to completely eradicate TB. Today we have at least 20 new diagnostic test platforms, 14 TB vaccine candidates in clinical trials and over 35 candidates in preclinical development, and among the antitubercular agents under clinical investigation, 4 anti-TB agents are in Phase III (efficacy) trials and 7 anti-TB agents are in Phase II, early bactericidal activity and sputum culture conversion trials (rifapentine is in a Phase II and a Phase III trial), 5 anti-TB agents in preclinical development and 3 anti-TB agents in Good Laboratory Practice toxicity evaluation. Recently US FDA has approved TMC207 as a part of combination therapy to treat adults with MDR pulmonary TB in the absence of other alternatives. We provide here the concise review on the chemical entities currently in the clinical trials, the new vaccines in the developmental pipeline, and the new diagnostic test.