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With the ability to cause massive epidemics that have consequences on millions of individuals globally, the Chikungunya virus (CHIKV) emerges as a severe menace. Developing an effective vaccine is urgent as no effective therapeutics are available for such viral infections. Therefore, we designed a novel mRNA vaccine against CHIKV with a combination of highly antigenic and potential MHC-I, MHC-II, and B-cell epitopes from the structural polyprotein. The vaccine demonstrated well-characterized physicochemical properties, indicating its solubility and potential functional stability within the body (GRAVY score of –0.639). Structural analyses of the vaccine revealed a well-stabilized secondary and tertiary structure (Ramachandran score of 82.8% and a Z-score of –4.17). Docking studies of the vaccine with TLR-2 (−1027.7 KJ/mol) and TLR-4 (−1212.4 KJ/mol) exhibited significant affinity with detailed hydrogen bond interactions. Molecular dynamics simulations highlighted distinct conformational dynamics among the vaccine, “vaccine-TLR-2” and “vaccine-TLR-4” complexes. The vaccine’s ability to elicit both innate and adaptive immune responses, including the presence of memory B-cells and T-cells, persistent B-cell immunity for a year, and the activation of TH cells leading to the release of IFN-γ and IL-2, has significant implications for its potential effectiveness. The CHIKV vaccine developed in this study shows promise as a potential candidate for future vaccine production against CHIKV, suggesting its suitability for further clinical advancement, including in vitro and in vivo experiments.

SARS-CoV-2, a novel Corona virus strain, was first detected in Wuhan, China, in December 2019. As of December 16, 2021, almost 4,822,472 people had died and over 236,132,082 were infected with this lethal viral infection. It is believed that the human immune system is thought to play a critical role in the initial phase of infection when the viruses invade the host cells. Although some effective vaccines have already been on the market, researchers and many bio-pharmaceuticals are still working hard to develop a fully functional vaccine or more effective therapeutic agent against the COVID-19. Other efforts, in addition to functional vaccines, can help strengthen the immune system to defeat the corona virus infection. Herein, we have reviewed some of those proven measures, following which a more efficient immune system can be better prepared to fight viral infection. Among these, dietary supplements like- fresh vegetables and fruits offer a plentiful of vitamins and antioxidants, enabling to build of a healthy immune system. While the pharmacologically active components of medicinal plants directly aid in fighting against viral infection, supplementary supplements combined with a healthy diet will assist to regulate the immune system and will prevent viral infection. In addition, some personal habits, like- regular physical exercise, intermittent fasting, and adequate sleep, had also been proven to aid the immune system in becoming an efficient one. Maintaining each of these will strengthen the immune system, allowing innate immunity to become a more defensive and active antagonistic mechanism against corona-virus infection. However, because dietary treatments take longer to produce beneficial effects in adaptive maturation, personalized nutrition cannot be expected to have an immediate impact on the global outbreak.

In marine ecosystems, dinoflagellates can become highly abundant and even dominant at times, despite their comparatively slow growth rates. One factor that may play a role in their ecological success is the production of complex secondary metabolite compounds that can have anti-predator, allelopathic, or other toxic effects on marine organisms, and also cause seafood poisoning in humans. Our knowledge about the genes involved in toxin biosynthesis in dinoflagellates is currently limited due to the complex genomic features of these organisms. Most recently, the sequencing of dinoflagellate transcriptomes has provided us with valuable insights into the biosynthesis of polyketide and alkaloid-based toxin molecules in dinoflagellate species. This review synthesizes the recent progress that has been made in understanding the evolution, biosynthetic pathways, and gene regulation in dinoflagellates with the aid of transcriptomic and other molecular genetic tools, and provides a pathway for future studies of dinoflagellates in this exciting omics era.

Helicobacter pylori infection of the stomach’s epithelial cells is a significant risk factor for stomach cancer. Various H pylori proteins (CagA, GGT, NapA, PatA, urease, and VacA) were targeted to design 2 messenger RNA (mRNA) vaccines, V1 and V2, using bioinformatics tools. Physicochemical parameters, secondary and tertiary structure, molecular docking and dynamic simulation, codon optimization, and RNA structure prediction have also been estimated for these developed vaccines. Physicochemical analyses revealed that these developed vaccines are soluble (GRAVY < 0), basic (pI < 7), and stable (aliphatic index < 80). The secondary and tertiary structure of the vaccines demonstrated robustness. The docking with toll-like receptors (TLRs) revealed that the vaccines have a potential affinity for TLR-2 (V1: −1132.3 kJ/mol, V2: −1093.6 kJ/mol) and TLR-4 (V1: −1042.7 kJ/mol, V2: −1201.2 kJ/mol), and molecular dynamics simulations confirmed their dynamic stability. Structural analyses of V1 (−505.96 kcal/mol) and V2 (−634.92 kcal/mol) mRNA vaccines underscored their stability. In addition, the vaccine showed a considerable rise in the counts of B cells and extended activation of both T cells was also observed for the vaccines, suggesting the potential for long-lasting immunity, and offering enhanced protection against H pylori. These findings not only suggest potential long-lasting immunity against H pylori but also offer hope for the future of stomach cancer prevention. Notably, the study emphasizes the need for subsequent animal and human-based studies to confirm these promising results.

Introduction: Coronavirus disease 2019 (COVID-19), caused by SARS-CoV-2, has had a disastrous effect worldwide during the previous three years due to widespread infections with SARS-CoV-2 and its emerging variations. More than 674 million confirmed cases and over 6.7 million deaths have been attributed to successive waves of SARS-CoV-2 infections as of 29th January 2023. Similar to other RNA viruses, SARS-CoV-2 is more susceptible to genetic evolution and spontaneous mutations over time, resulting in the continual emergence of variants with distinct characteristics. Spontaneous mutations of SARS-CoV-2 variants increase its transmissibility, virulence, and disease severity and diminish the efficacy of therapeutics and vaccines, resulting in vaccine-breakthrough infections and re-infection, leading to high mortality and morbidity rates. Materials and methods: In this study, we evaluated 10,531 whole genome sequences of all reported variants globally through a computational approach to assess the spread and emergence of the mutations in the SARS-CoV-2 genome. The available data sources of NextCladeCLI 2.3.0 ( https://clades.nextstrain.org/ ) and NextStrain ( https://nextstrain.org/ ) were searched for tracking SARS-CoV-2 mutations, analysed using the PROVEAN, Polyphen-2, and Predict SNP mutational analysis tools and validated by Machine Learning models. Result: Compared to the Wuhan-Hu-1 reference strain NC 045512.2, genome-wide annotations showed 16,954 mutations in the SARS-CoV-2 genome. We determined that the Omicron variant had 6,307 mutations (retrieved sequence:1947), including 67.8% unique mutations, more than any other variant evaluated in this study. The spike protein of the Omicron variant harboured 876 mutations, including 443 deleterious mutations. Among these deleterious mutations, 187 were common and 256 were unique non-synonymous mutations. In contrast, after analysing 1,884 sequences of the Delta variant, we discovered 4,468 mutations, of which 66% were unique, and not previously reported in other variants. Mutations affecting spike proteins are mostly found in RBD regions for Omicron, whereas most of the Delta variant mutations drawn to focus on amino acid regions ranging from 911 to 924 in the context of epitope prediction (B cell & T cell) and mutational stability impact analysis protruding that Omicron is more transmissible. Discussion: The pathogenesis of the Omicron variant could be prevented if the deleterious and persistent unique immunosuppressive mutations can be targeted for vaccination or small-molecule inhibitor designing. Thus, our findings will help researchers monitor and track the continuously evolving nature of SARS-CoV-2 strains, the associated genetic variants, and their implications for developing effective control and prophylaxis strategies.

In 2016, 2017 and 2018, elevated levels of the species Alexandrium pacificum were detected within a blue mussel (Mytilus galloprovincialis) aquaculture area at Twofold Bay on the south coast of New South Wales, Australia. In 2016, the bloom persisted for at least eight weeks and maximum cell concentrations of 89,000 cells L−1 of A. pacificum were reported. The identity of A. pacificum was confirmed using molecular genetic tools (qPCR and amplicon sequencing) and complemented by light and scanning electron microscopy of cultured strains. Maximum reported concentrations of paralytic shellfish toxins (PSTs) in mussel tissue was 7.2 mg/kg PST STX equivalent. Elevated cell concentrations of A. pacificum were reported along the adjacent coastal shelf areas, and positive PST results were reported from nearby oyster producing estuaries during 2016. This is the first record of PSTs above the regulatory limit (0.8 mg/kg) in commercial aquaculture in New South Wales since the establishment of routine biotoxin monitoring in 2005. The intensity and duration of the 2016 A. pacificum bloom were unusual given the relatively low abundances of A. pacificum in estuarine and coastal waters of the region found in the prior 10 years.

Helicobacter pylori infection of the stomach’s epithelial cells is a significant risk factor for stomach cancer. Various H pylori proteins (CagA, GGT, NapA, PatA, urease, and VacA) were targeted to design 2 messenger RNA (mRNA) vaccines, V1 and V2, using bioinformatics tools. Physicochemical parameters, secondary and tertiary structure, molecular docking and dynamic simulation, codon optimization, and RNA structure prediction have also been estimated for these developed vaccines. Physicochemical analyses revealed that these developed vaccines are soluble (GRAVY < 0), basic (pI < 7), and stable (aliphatic index < 80). The secondary and tertiary structure of the vaccines demonstrated robustness. The docking with toll-like receptors (TLRs) revealed that the vaccines have a potential affinity for TLR-2 (V1: −1132.3 kJ/mol, V2: −1093.6 kJ/mol) and TLR-4 (V1: −1042.7 kJ/mol, V2: −1201.2 kJ/mol), and molecular dynamics simulations confirmed their dynamic stability. Structural analyses of V1 (−505.96 kcal/mol) and V2 (−634.92 kcal/mol) mRNA vaccines underscored their stability. In addition, the vaccine showed a considerable rise in the counts of B cells and extended activation of both T cells was also observed for the vaccines, suggesting the potential for long-lasting immunity, and offering enhanced protection against H pylori . These findings not only suggest potential long-lasting immunity against H pylori but also offer hope for the future of stomach cancer prevention. Notably, the study emphasizes the need for subsequent animal and human-based studies to confirm these promising results.

Species of the genus Alexandrium are one of the most studied dinoflagellates due to their production of the neurotoxins, Paralytic Shellfish Toxins (PSTs). PST-associated Harmful Algal Blooms (HABs) appear to be increasing around the world. The appearance of species of Alexandrium is now frequent in coastal waters of Australia, particularly in Tasmania and New South Wales. The East Australian Current (EAC) flows southward along the coasts of eastern Australia and has been reported as a global ‘climate change hotspot’. Despite such potent neurotoxin production, the ecology, toxicity and population dynamics of AlexaAlexandriumspecies are little known in Australia.In this thesis, I have investigated the first record of PST above the regulatory limit of 0.8 mg/kg produced by Alexandrium pacificum in the commercial aquaculture area of south-eastern Australia. During this unprecedented event, the maximum reported PST concentration in mussel tissue was 7.2 mg/kg STX equivalent. A comparative differential gene expression study was conducted to understand the gene regulation of PST related genes in Alexandrium pacificum. In this study, experiments were performed in the presence and absence of the copepodamide-synthesizing copepod Parvocalanus crassirostris. Using Nanostring gene technology, results identified the up-regulation of the key PST-related gene sxtA, in particular, one paralogue each of domains of sxtA1 and sxtA4. An increased rate of PST production in the two PST-producing strains in the presence of copepods was identified, however it did not influence gene related transcript abundance. This indicated that post-transcriptional regulation processes may be important in regulating PST production in Alexandrium pacificum. In this thesis, the population structure of Alexandrium pacificum was examined in different Australia boundaries currents – the East Australian Current (EAC) and the Leeuwin Current (LC). This study was conducted using Single Nucleotide Polymorphisms (SNPs) as genetic markers and represents the first time the population structure of a phytoplankton species has been examined in Australian waters. Strains from South Australia and Western Australia clustered as a group, and were separated from the strains isolated from the EAC region, indicating the presence of genetic isolation of A. pacificum strains in Australian waters. It suggests that A. pacificumis more likely to represent a long resident population, and it is not a recent bioinvasion in Western Australian waters.The results identified during this study significantly advance the understanding of Alexandrium, especially their abundance, diversity, population structure and the regulation of the PST-related genes.

The application of meta-barcoding, qPCR, and metagenomics to aquatic eukaryotic microbial communities requires knowledge of genomic copy number variability (CNV). CNV may be particularly relevant to functional genes, impacting dosage and expression, yet little is known of the scale and role of CNV in microbial eukaryotes. Here, we quantify CNV of rRNA and a gene involved in Paralytic Shellfish Toxin (PST) synthesis (sxtA4), in 51 strains of 4 Alexandrium (Dinophyceae) species. Genomes varied up to threefold within species and ~7-fold amongst species, with the largest (A. pacificum, 130 ± 1.3 pg cell−1 /~127 Gbp) in the largest size category of any eukaryote. Genomic copy numbers (GCN) of rRNA varied by 6 orders of magnitude amongst Alexandrium (102– 108 copies cell−1) and were significantly related to genome size. Within the population CNV of rRNA was 2 orders of magnitude (105 – 107 cell−1) in 15 isolates from one population, demonstrating that quantitative data based on rRNA genes needs considerable caution in interpretation, even if validated against locally isolated strains. Despite up to 30 years in laboratory culture, rRNA CNV and genome size variability were not correlated with time in culture. Cell volume was only weakly associated with rRNA GCN (20–22% variance explained across dinoflagellates, 4% in Gonyaulacales). GCN of sxtA4 varied from 0–102 copies cell−1, was significantly related to PSTs (ng cell−1), displaying a gene dosage effect modulating PST production. Our data indicate that in dinoflagellates, a major marine eukaryotic group, low-copy functional genes are more reliable and informative targets for quantification of ecological processes than unstable rRNA genes.