Reverse vaccinology and immunoinformatics approach to design a chimeric epitope vaccine against Orientia tsutsugamushi.

Scrub typhus is a vector-borne infectious disease caused by Orientia tsutsugamushi and it is reportedly associated with up to 20 % of hospitalized cases of febrile illnesses. The major challenge of vaccine development is the lack of identified antigens that can induce both heterotypic and homotypic immunity including the production of antibodies, cytotoxic T lymphocyte, and helper T lymphocytes. We employed a comprehensive immunoinformatic prediction algorithm to identify immunogenic epitopes of the 56-kDa type-specific cell membrane surface antigen and surface cell antigen A of O. tsutsugamushi to select potential candidates for developing vaccines and diagnostic assays. We identified 35 linear and 29 continuous immunogenic B-cell epitopes and 51 and 27 strong-binding T-cell epitopes of major histocompatibility complex class I and class II molecules, respectively, in the conserved and variable regions of the 56-kDa type-specific surface antigen. The predicted B- and T-cell epitopes were used to develop immunogenic multi-epitope candidate vaccines and showed to elicit a broad-range of immune protection. A stable interactions between the multi-epitope vaccines and the host fibronectin protein were observed using docking and simulation methods. Molecular dynamics simulation studies demonstrated that the multi-epitope vaccine constructs and fibronectin docked models were stable during simulation time. Furthermore, the multi-epitope vaccine exhibited properties such as antigenicity, non-allergenicity and ability to induce interferon gamma production and had strong associations with their respective human leukocyte antigen alleles of world-wide population coverage. A correlation of immune simulations and the in-silico predicted immunogenic potential of multi-epitope vaccines implicate for further investigations to accelerate designing of epitope-based vaccine candidates and chimeric antigens for development of serological diagnostic assays for scrub typhus.

Metal-free S-arylation of 5-mercaptotetrazoles and 2-mercaptopyridine with unsymmetrical diaryliodonium salts.

Herein, we demonstrate the application of unsymmetrical iodonium salts towards S-arylation of heterocyclic thiols (especially tetrazole-5-thiols and pyridine-2-thiol) under metal-free conditions, affording a diverse range of di(hetero)aryl thioethers in moderate to good yields. A detailed study on the effects of counter-anions and the auxiliary of iodonium salts was conducted. Suitable auxiliary selection of the unsymmetrical iodonium salt offers flexibility for a wide range of aryl moieties and its incorporation into S-arylation. The DFT study supports the experimental observations of chemoselective arylation.

Tropospheric degradation of 2-fluoropropene (CH3CFCH2) initiated by hydroxyl radical: Reaction mechanisms, kinetics and atmospheric implications from DFT study.

Degradation of hydrofluoro-olefins (HFOs) with oxidants plays a significant role in the troposphere. Thus, we have investigated detail theoretical calculations of hydroxyl radical (•OH) initiated oxidation of 2-fluoropropene (CH3CFCH2) using M06-2X/6-311++G(d,p) level of theory. Here, we have considered different possible H-abstraction and OH addition for the degradation of CH3CFCH2 molecule. The potential energy analysis shows that OH-addition channels are more dominant than H-abstraction channels. The calculated reaction enthalpies (ΔrH°) and Gibbs free energies (ΔrG°) also suggest that OH-addition reaction channels are more favourable than H-abstraction channels. The overall rate coefficients for CH3CFCH2 + â€¢OH reaction is calculated within the temperature range of 250-450 K. The observed overall rate coefficient (2.01 × 10-11 cm3 molecule-1 s-1) at 298 K for the titled reaction is found to be in good agreement with the earlier reported experimental rate coefficient. The calculated percentage branching ratio shows that the contribution of OH-addition to α-carbon and ß-carbon of CH3CFCH2 molecule are 85.10% and 14.20% to the overall rate coefficient while H-abstractions have a negligible contribution. Based on the kinetics calculations, the atmospheric lifetime of the titled molecule is found to be 0.6 days. Further, we have also explored the degradation pathways of OH-addition product radicals and found acetyl fluoride (CH3CFO) and formaldehyde (HCHO) are the end degradation products.

Quantum mechanical study on the oxidation of ethyl vinyl ketone initiated by an OH radical.

Oxidation of ethyl vinyl ketone (CH2CHCOCH2CH3) by an OH radical was carried out using the M06-2X/6-311++G(d,p) level of theory. For the OH-initiated oxidation of ethyl vinyl ketone (EVK), we have considered six H-atom abstractions and three addition reactions. From the energetic calculation of the species involved therein, the potential energy surface (PES) of all the reaction channels was constructed. From the energy profile, we found that the H-atom abstraction from the methylene group (-CH2-) of CH2CHCOCH2CH3 is energetically more favourable than the other H-abstraction channels. Moreover, we also observed that OH-addition to the α-carbon of the carbon-carbon double bond of the title molecule is energetically and thermodynamically more dominant than ß-carbon and carbonyl carbon. The rate coefficients for all the reaction channels were calculated using the canonical transition state theory at the temperature range of 250-450 K and it reveals that among all the reaction channels, OH-addition to α-carbon is kinetically more dominant to the total rate constant. The total rate coefficient for the reaction at 298 K is found to be in good agreement with the reported experimental rate constant. Finally, we have determined the atmospheric lifetime of the title molecule.