Biology subjects

Simmini, S.

Publications and source records attributed to Simmini, S..

3 recordsLinked to original sources

bioRxiv2026

Human airway organoids as a high-throughput screening platform for antiviral natural products discovery

Antiviral drug discovery for respiratory viruses is hindered by the lack of scalable physiologically relevant systems. Here, we report the first high-throughput screen of 764 natural plant extracts against respiratory syncytial virus (RSV) using human primary airway organoids as a relevant model. A parallel screen conducted in A549 cells allowed the identification of 70 extracts with organoid-specific antiviral activity from which 45 active phytocompounds were purified. We identified early- and late-acting antiviral compounds and demonstrated a polarization-dependent activity for some of them. Collectively, our results establish the use of airway organoids as a scalable first-line platform for high-throughput antiviral discovery and exploit the plant-derived chemical space as an underexplored source of RSV inhibitors.

microbiology↗

bioRxiv2025

Generation of apical-out nasal organoids to facilitate viral infection and drug screening

Advanced culture systems such as organoids can serve as powerful platforms to study epithelial physiology, as they recapitulate the organisation and many key functions of the tissue of origin. The nasal epithelium is the first respiratory epithelium that is exposed to inhaled airborne pathogens. As a result, it is crucial to model host-pathogen interactions occurring in this tissue. To facilitate the efficient modelling of these interactions, we have developed a method to generate de novo apical-out nasal organoids from nasal epithelial cell aggregates. Optimisation of this method revealed a stark tissue-specific effect of the culture temperature, as apical-out nasal organoids were generated in much higher efficiency at 32.5 {degrees}C, compared to more widely used temperatures of 37{degrees}C. These organoids are composed of ciliated, basal and goblet cells and are produced in a completely standardised and scalable manner, devoid of any extracellular matrix hydrogel. Moreover, they displayed high homogeneity in size and cellular composition, as well as susceptibility to viral infections and capability to model antiviral drug responses. Here, we describe a method for the efficient and reproducible generation of apical-out nasal organoids with high potential to be utilised in host-pathogen interaction studies and personalised medicine from easy-to-access nasal swabs.

cell biology↗

bioRxiv2024

A Human Biomimetic Intestinal Mucosa Model to Study Gastrointestinal Development and Disease

The intestinal mucosa plays a vital role in nutrient absorption, drug metabolism, and pathogen defence. Advances in single-cell technologies have highlighted the specialised roles of various cell types that execute these diverse functions. Aside from intestinal epithelial cells, fibroblasts play an essential role in regulating the extracellular matrix and controlling pro- inflammatory signalling, and antigen-presenting cells (macrophages and dendritic cells) maintain intestinal homeostasis and immune responses. The incorporation of such cellular complexity within the existing in vitro models of the human intestine is currently challenging. To address this, we developed a human intestinal model that accurately mimics the mucosal cellular environment comprising intestinal epithelial cells, intestinal fibroblasts, and antigen presenting cells. This model includes co-cultures of adult and foetal cells, facilitating studies on barrier function, inflammation, and viral infections. It replicates extracellular matrix deposition, Paneth cell differentiation, immune interactions, and can be used to model host- pathogen interactions. Our advanced co-culture model improves the physiological relevance of in vitro studies, enabling the exploration of epithelial-mesenchymal-immune crosstalk and its role in intestinal health and disease.

cell biology↗