Next-Generation Vaccines: Nanovaccines in the Fight against SARS-CoV-2 Virus and beyond SARS-CoV-2.

The virus responsible for the coronavirus viral pandemic is the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Emerging SARS-CoV-2 variants caused by distinctive mutations within the viral spike glycoprotein of SARS-CoV-2 are considered the cause for the rapid spread of the disease and make it challenging to treat SARS-CoV-2. The manufacturing of appropriate efficient vaccines and therapeutics is the only option to combat this pandemic. Nanomedicine has enabled the delivery of nucleic acids and protein-based vaccines to antigen-presenting cells to produce protective immunity against the coronavirus. Nucleic acid-based vaccines, particularly mRNA nanotechnology vaccines, are the best prevention option against the SARS-CoV-2 pandemic worldwide, and they are effective against the novel coronavirus and its multiple variants. This review will report on progress made thus far with SARS-CoV-2 vaccines and beyond employing nanotechnology-based nucleic acid vaccine approaches.

Efficient discrimination of natural stereoisomers of chicoric acid, an HIV-1 integrase inhibitor.

Plants from the Asteraceae family are known to contain a wide spectrum of phytochemicals with various nutraceutical properties. One important phytochemical, chicoric acid (CA), is reported to exist in plants, such as Sonchus oleraceus and Bidens pilosa, as stereoisomers. These CA molecules occur either as the naturally abundant RR-chicoric acid (RR-CA), or the less abundant RS-chicoric acid (RS-CA), also known as meso-chicoric acid. To date, little is known about the biological activity of RS-CA, but there is evidence of its anti-human immunodeficiency virus (HIV) properties. In this study, a reliable analytical method was developed to distinguish between the two stereoisomers detected in S. oleraceus and B. pilosa. For structure identification and characterization of CA molecules, liquid chromatography-mass spectrometry (LC-MS) was used in combination with ultraviolet radiation (UV)-induced geometrical isomerization, molecular dynamics (MD) simulations, and density functional theory (DFT) models. Optimized structures from DFT calculations were used for docking studies against the HIV-1 integrase enzyme. Different retention times on the reverse phase chromatograms revealed that the plants produce two different CA stereoisomers: S. oleraceus produced the RR-CA isomer, while B. pilosa produced the RS-CA isomer. DFT results demonstrated the RR-CA molecule was more stable than RS-CA due to the stabilizing force of intra-molecular hydrogen bonding. Differences in the HIV-1 integrase enzyme binding modes were observed, with the RR-CA being a more potent inhibitor than the RS-CA molecule. The results highlight the significance of plant metabolite structural complexity from both chemical and biological perspectives. Furthermore, the study demonstrates that induced-formation of geometrical isomers, in combination with the predictive ability of DFT models and the resolving power of the LC-MS, can be exploited to distinguish structurally closely related compounds, such as stereoisomers.

Highlighting mass spectrometric fragmentation differences and similarities between hydroxycinnamoyl-quinic acids and hydroxycinnamoyl-isocitric acids.

BACKGROUND: Plants contain a myriad of metabolites which exhibit diverse biological activities. However, in-depth analyses of these natural products with current analytical platforms remains an undisputed challenge due to the multidimensional chemo-diversity of these molecules, amplified by both isomerization and conjugation. In this study, we looked at molecules such as hydroxyl-cinnamic acids (HCAs), which are known to exist as positional and geometrical isomers conjugated to different organic acids namely quinic- and isocitric acid. OBJECTIVE: The study aimed at providing a more defined distinction between HCA conjugates from Amaranthus viridis and Moringa oleifera, using mass spectrometry (MS) approaches. METHODS: Here, we used a UHPLC-MS/MS targeted approach to analyze isobaric HCA conjugates extracted from the aforementioned plants. RESULTS: Mass spectrometry results showed similar precursor ions and fragmentation pattern; however, distinct differences were seen with ions at m/z 155 and m/z 111 which are associated with isocitric acid conjugates. CONCLUSION: Our results highlight subtle differences between these two classes of compounds based on the MS fingerprints, enabling confidence differentiation of the compounds. Thus, these findings provide a template reference for accurate and confident annotation of such compounds in other plants.