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Molecular hybridization approach is an emerging tool in drug discovery for designing new pharmacophores with biological activity. A novel, new series of coumarin–benzimidazole hybrids were designed, synthesized and evaluated for their broad spectrum antimicrobial activity. Among all the synthesized molecules, compound ( E )-3-(2-1 H -benzo[ d ]imidazol-1-yl)-1-((4-chlorobenzyl)oxy)imino)ethyl)-2 H -chromen-2-one showed the most promising broad spectrum antibacterial activity against Pseudomonas aeruginosa , Staphylococcus aureus, Bacillus subtilis and Proteus vulgaris. In addition, it has showed no cytotoxicity and hemolysis at 10 times the MIC concentration. SAR studies indicate that position of the chlorine atom in the hybrid critically determines the antibacterial activity.

Worldwide, TB is one of the deadly airborne diseases, which accounts for 10.4 million deaths annually. Serious toxicity issue, prolonged treatment regimens of the current drugs, rise in multidrug-resistant strains, and the unique defensive mechanism makes the development of novel therapeutic molecules against Mycobacterium tuberculosis (MT) an urgent need. As MT has a lengthy latent phase and unique cell wall architecture, a reasonable approach is needed to find molecules having a different killing mechanism rather than traditional approaches. Host defence peptides (HDPs) will be the most promising alternative, potential therapeutic candidates as they target the microbial membrane in particular and are an essential part of the innate immunity of humans. This works demonstrates the utility of “Database filtering” and three-dimensional (3D) modelling approach in finding novel AMPs with appreciable activity towards MT. Results of this study indicate that peptides with 70% hydrophobicity, but without hydrophobicity patches (> 4 hydrophobic amino acids in series) and charge of + 4 or + 5 are most likely to be good anti-tubercular candidates.

SARS-CoV-2 immunity and innate immune training may influence influenza vaccine immunogenicity. We investigated this in India. Adult volunteers with hybrid SARS-CoV-2 immunity were administered Fluarix TM Tetra (GlaxoSmithKlein) 2022/2023 NH Vaccine in 2022. Significant induction of hemagglutinin inhibition-specific antibodies and polyfunctional central memory CD4 + T-cells (TCM) were observed 1-week post-vaccination with variable induction of CD8 + T-cell and innate effectors. Vaccination also expanded Flu-specific regulatory T-cells (Treg), which negatively correlated with CD4 responses, highlighting vaccine immunogenicity may be subject to Treg dampening. Fluarix TM did not boost SARS-CoV-2 immunity. However, SARS-CoV-2-specific T-cell responses correlated positively with vaccine-induced T-cell responses. We evaluated trained immunity post-COVID-19 as a potential regulatory mechanism linking SARS-CoV-2 and heterologous vaccine immunogenicity. We observed, elevated frequencies of basal bacterial Lipopolysaccharide (LPS)-induced IL-6 + IL1β + HLA-DR + CD14 + CD16 - frequencies post-COVID-19 correlated positively with vaccine-induced Fluarix-specific CD4 T-cell frequencies. Our study highlights a potential positive role for COVID-19-driven immune imprinting on heterologous vaccine immunogenicity in a post-COVID-19 era.

Background: The COVID-19 pandemic prompted unprecedented vaccine development efforts against SARS-CoV-2. India, which was one of the countries most impacted by COVID-19, developed its indigenous vaccine in addition to utilizing the ones developed by other countries. While antibody levels and neutralizing antibody titres are considered initial correlates of immune protection, long-term protection from the pathogen relies on memory B and T cells and their recall responses. In this regard, global research has primarily focused on mRNA-based vaccines. The studies on immune memory response, particularly B cell memory response induced by the vaccines given to Indians, remain relatively obscure. Methods: We assessed Receptor Binding Domain-specific memory B cells in the peripheral circulation and their ability to secrete antigen-specific antibodies among Indians vaccinated with Covaxin (BBV152), Covishield (AZD1222), Corbevax (BECOV2D), and Sputnik Light, as well as unvaccinated individuals. Results: Corbevax and Sputnik Light conferred better antibody-secreting cell (ASC) responses over time compared to other groups. Conclusions: These findings contribute to our understanding of vaccine-induced immune memory in the Indian population; providing insights that could inform future vaccine strategies.

Immunogens mimicking the native-like structure of surface-exposed viral antigens are considered promising vaccine candidates. Influenza viruses are important zoonotic respiratory viruses with high pandemic potential. Recombinant soluble hemagglutinin (HA) glycoprotein-based protein subunit vaccines against Influenza have been shown to induce protective efficacy when administered intramuscularly. Here, we have expressed a recombinant soluble trimeric HA protein in Expi 293F cells and purified the protein derived from the Inf A/Guangdong-Maonan/ SWL1536/2019 virus which was found to be highly virulent in the mouse. The trimeric HA protein was found to be in the oligomeric state, highly stable, and the efficacy study in the BALB/c mouse challenge model through intradermal immunization with the prime-boost regimen conferred complete protection against a high lethal dose of homologous and mouse-adapted InfA/PR8 virus challenge. Furthermore, the immunogen induced high hemagglutinin inhibition (HI) titers and showed cross-protection against other Inf A and Inf B subtypes. The results are promising and warrant trimeric HA as a suitable vaccine candidate.

Silver is an agent used for different wounds and ulcer treatment as it is nontoxic. However, silver in an ionic or Nanoparticles form is highly toxic to microorganisms. Hence, silver Nanoparticles has wide range of applications than silver ion. Over the physical and chemical methods green synthesis is eco-friendly and cost effective. The present study reveals the formation of silver Nanoparticles by using the fruit extract (Ananas Comosus) by observing the colour change. The produced nanoparticles are characterized by the physicochemical techniques, X-ray diffraction, UV-Visible and antimicrobial activity. The diffraction peaks attributed to 2θ values of 38.11˚ and 44.27˚ (111, 200) reveals the formation of silver nanoparticles. UV-Vis spectrophotometer shows Surface Plasmon resonance (SPR) at 459 nm. The antibacterial studies promise the formation of silver nanoparticle with the ability to inhibit growth of Escherichia coli.