Proteome Based Approach Defines Candidates for Designing a Multitope Vaccine against the Nipah Virus.

Nipah virus is one of the most harmful emerging viruses with deadly effects on both humans and animals. Because of the severe outbreaks, in 2018, the World Health Organization focused on the urgent need for the development of effective solutions against the virus. However, up to date, there is no effective vaccine against the Nipah virus in the market. In the current study, the complete proteome of the Nipah virus (nine proteins) was analyzed for the antigenicity score and the virulence role of each protein, where we came up with fusion glycoprotein (F), glycoprotein (G), protein (V), and protein (W) as the candidates for epitope prediction. Following that, the multitope vaccine was designed based on top-ranking CTL, HTL, and BCL epitopes from the selected proteins. We used suitable linkers, adjuvant, and PADRE peptides to finalize the constructed vaccine, which was analyzed for its physicochemical features, antigenicity, toxicity, allergenicity, and solubility. The designed vaccine passed these assessments through computational analysis and, as a final step, we ran a docking analysis between the designed vaccine and TLR-3 and validated the docked complex through molecular dynamics simulation, which estimated a strong binding and supported the nomination of the designed vaccine as a putative solution for Nipah virus. Here, we describe the computational approach for design and analysis of this vaccine.

Formulation and in vitro characterization of poly(dl-lactide-co-glycolide)/Eudragit RLPO or RS30D nanoparticles as an oral carrier of levofloxacin hemihydrate.

The main objective of this study was to design positively charged Levofloxacin Hemihydrate (Levo-h)-loaded nanoparticles with improved entrapment efficiency and antibacterial activity. PLGA alone or in combinations with Eudragit® RLPO or RS30D with or without positively charged inducing agent; 1,2-dioleoyl-3-trimethylammonium-propane, chloride salt (DOTAP); were used for preparation of nanoparticles. Blending between PLGA and Eudragit® RLPO or RS30D with inclusion of DOTAP caused a marked increase in entrapment efficiency and switched zeta potential from negative to positive. Nanoparticle formulations; NR3 (Levo-h:PLGA:Eudragit® RLPO; 1:1:1 w/w with DOTAP) and NS3 (Levo-h:PLGA:Eudragit® RS30D; 1:1:1 w/w with DOTAP) that possess high positive zeta potential (59.3 ± 7.5 and 55.1 ± 8.2 mV, respectively) and Efficient Levo-h entrapment (89.54 ± 1.5 and 77.65 ± 1.8%, respectively) were selected for further examinations; in vitro release, physical stability and microbiological study. NR3 and NS3 showed significant sustained release of Levo-h. NR3 and NS3 exhibited good stability after storage at room temperature. Microbiological assay showed strengthened antibacterial activity of NR3 against both types of gram-negative bacteria (E. coli, Ps. aeruginosa) and of NS3 against Ps. aeruginosa compared to free Levo-h solution. NR3 and NS3 appear to be promising oral delivery system for Levo-h.

Sodium Citrate Alleviates Virulence in Pseudomonas aeruginosa.

The development of bacterial resistance is an insistent global health care issue, especially in light of the dwindled supply of new antimicrobial agents. This mandates the development of new innovative approaches to overcome the resistance development obstacle. Mitigation of bacterial virulence is an interesting approach that offers multiple advantages. Employing safe chemicals or drugs to mitigate bacterial virulence is an additive advantage. In the current study, the in vitro antivirulence activities of citrate were evaluated. Significantly, sodium citrate inhibited bacterial biofilm formation at sub-MIC concentrations. Furthermore, sodium citrate decreased the production of virulence factors protease and pyocyanin and diminished bacterial motility. Quorum sensing (QS) is the communicative system that bacterial cells utilize to communicate with each other and regulate the virulence of the host cells. In the present study, citrate in silico blocked the Pseudomonas QS receptors and downregulated the expression of QS-encoding genes. In conclusion, sodium citrate showed a significant ability to diminish bacterial virulence in vitro and interfered with QS; it could serve as a safe adjuvant to traditional antibiotic treatment for aggressive resistant bacterial infections such as Pseudomonas aeruginosa infections.

In Silico Designing of a Multitope Vaccine against Rhizopus microsporus with Potential Activity against Other Mucormycosis Causing Fungi.

During the current era of the COVID-19 pandemic, the dissemination of Mucorales has been reported globally, with elevated rates of infection in India, and because of the high rate of mortality and morbidity, designing an effective vaccine against mucormycosis is a major health priority, especially for immunocompromised patients. In the current study, we studied shared Mucorales proteins, which have been reported as virulence factors, and after analysis of several virulent proteins for their antigenicity and subcellular localization, we selected spore coat (CotH) and serine protease (SP) proteins as the targets of epitope mapping. The current study proposes a vaccine constructed based on top-ranking cytotoxic T lymphocyte (CTL), helper T lymphocyte (HTL), and B cell lymphocyte (BCL) epitopes from filtered proteins. In addition to the selected epitopes, ß-defensins adjuvant and PADRE peptide were included in the constructed vaccine to improve the stimulated immune response. Computational tools were used to estimate the physicochemical and immunological features of the proposed vaccine and validate its binding with TLR-2, where the output data of these assessments potentiate the probability of the constructed vaccine to stimulate a specific immune response against mucormycosis. Here, we demonstrate the approach of potential vaccine construction and assessment through computational tools, and to the best of our knowledge, this is the first study of a proposed vaccine against mucormycosis based on the immunoinformatics approach.

Serum Vitamin D Levels in Chronic Hepatitis B Patients Before and During Treatment.

BACKGROUND & AIMS: Hepatitis B is a potentially life-threatening liver infection and it is a major global health problem. Over the past decade, numerous studies have reported that patients with CLD, especially HCV-positive and HBV-positive patients, have decreased 25(OH) D levels. The current study was designed to assess the serum levels of vitamin D [25(OH) D3] in chronic hepatitis B patients, before and during treatment with antiviral therapy. METHODS: It was a prospective study in which 80 subjects were enrolled between December 2017 and June 2018. A total of 50 treatment-naïve chronic HBV patients and 30 healthy subjects were recruited. The studied cases received treatment in the form of Lamivudine 100 mg tablet, once daily. Full routine laboratory investigations, HBV DNA measurement by real-time PCR were conducted once before initiation of antiviral treatment and again at least 6 months later. Serum vitamin D level [25(OH)D3 was assessed twice, once before initiation of antiviral treatment and again at least 6 months later. This was done for all the patients enrolled in the study. RESULTS: The studied cases showed a significantly low mean serum Vitamin D level when assessed before treatment (21.6 ± 5.8 ng/ml), compared to the level after 6 ms of treatment (31.1 ± 7.3 ng/ml) which was comparable to that of the control group (33.4 ± 5 ng/ml). CONCLUSION: The present study highlights the impact of antiviral therapy on vitamin D deficiency in CHB patients, where effective therapy improves vitamin D levels. Meanwhile, it is recommended to study the impact of vitamin D replacement and correction on the disease progression or regression.