New approach for anti-RSV compound discovery

The respiratory syncytial virus (RSV) has been identified as a major causative agent of bronchiolitis in children; nevertheless, available therapeutic options remain limited. Natural products (NPs) have been valued in the field of drug discovery and hold great promise for addressing this gap. However, there is a lack of methodologies that combine high-throughput screening (HTS) of natural extracts (NEs) with parallel metabolomic profiling to target the isolation of potential antivirals. This study presents an antiviral discovery approach that integrates HTS of 192 NEs against RSV in human lung adenocarcinoma cells (A549) with their systematic metabolite profiling. To optimise the identification of compounds with antiviral activity, they developed a scoring system, referred to as the "bioscore". This score correlates the antiviral activity of each NE with the normalised intensities of its constituents across the 192 NEs. Using this approach, triterpenes, including betulinic acid (BA), were frequently identified in active NEs, contributing to a high hit rate of 38 %. After isolating BA from Pilea plataniflora, the authors confirmed its antiviral activity in A549 cells, as well as in physiologically relevant models such as airway organoids and human airway epithelia cultured at the air-liquid interface. They further investigated its mechanism of action and found an effect at the early stage of viral replication. Protoapigenone, a species-specific flavonoid from this set of 192 NEs, was also identified as a potential antiviral NP, though limited by its cytotoxicity. This integrative workflow enables scalable antiviral screening of NEs by directly linking metabolomics with bioactivity through bioscore-driven prioritisation.

Full article: https://doi.org/10.1016/j.biopha.2025.118917

WHY IS IT IMPORTANT?

Respiratory syncytial virus (RSV) is a leading cause of severe lung infections in infants, young children, and older adults. Despite vaccines and preventive antibodies, treatment options for people who are already infected are very limited. This study is important because it proposes a faster and smarter way to discover new antiviral drugs from plants, a rich but underused source of medicines. By combining high-throughput testing of plant extracts with advanced chemical analysis, the researchers identified betulinic acid, a natural compound, as an effective inhibitor of RSV. Importantly, it worked not only in simple cell models but also in advanced models that closely mimic the human airway. This approach could accelerate the discovery of affordable antiviral treatments, potentially improving care for vulnerable populations affected by RSV worldwide.

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