Bailly, B. | bioRxiv Science

bioRxiv2025

Human parainfluenza virus infection remodels the host cell glycome

Human parainfluenza virus type 3 (HPIV-3) remains a major cause of respiratory illness particularly among young children, the elderly and immunocompromised individuals. Despite significant efforts in therapeutic discovery research, there is neither an effective antiviral nor a vaccine available against HPIV-3. Host cell glycosylation is known to play a pivotal role in virus entry and replication. While some host glycan-based cellular receptors for HPIV-3 have been identified, the dynamics of the host glycome upon HPIV-3 infection has never been studied. Herein, we report the first mass spectrometry-based study that provides direct insight into the remodelling of the human lung adenocarcinoma cell (A549) glycome upon HPIV-3 infection. In this study we observed that HPIV-3 infection led to significant host-cell glycome changes in both oligomannose and sialylated complex-type N-glycans. Moreover, notable changes were also observed in both core 1 and core 2 type O-glycans, along with distinct glycosphingolipid remodelling in infected cells compared to their mock-infected counterparts. Our study presents the first evidence that hPIV-3 infection alters host-cell glycome, offering new insights into the viruss impact on host cellular processes.

microbiology↗

bioRxiv2022

Drug repurposing for therapeutic discovery against human metapneumovirus infection

Human metapneumovirus (HMPV) is recognised as an important cause of pneumonia in infants, elderly, and immunocompromised individuals worldwide. The absence of an antiviral treatment or vaccine strategy against HMPV infection creates a high burden on the global health care system. Drug repurposing has become increasingly attractive for the treatment of emerging and endemic diseases as it requires less research and development costs than traditional drug discovery. In this study, we developed an in vitro medium-throughput screening assay that allows for the identification of novel anti-HMPV drugs candidates. Out of [~]2400 compounds, we identified eleven candidates with a dose-dependent inhibitory activity against HMPV infection. Additionally, we further described the mode of action of five anti-HMPV candidates with low in vitro cytotoxicity. Two entry inhibitors, Evans Blue and aurintricarboxylic acid, and three post-entry inhibitors, mycophenolic acid, mycophenolate mofetil, and 2,3,4-trihydroxybenzaldehyde, were identified. Among them, the mycophenolic acid series displayed the highest levels of inhibition, due to the blockade of intracellular guanosine synthesis. Importantly, MPA has significant potential for drug repurposing as inhibitory levels are achieved below the approved human oral dose. Our drug-repurposing strategy proved to be useful for the rapid discovery of novel hit candidates to treat HMPV infection and provide promising novel templates for drug design. HighlightsO_LIThere is currently no treatment against acute HMPV infection. C_LIO_LIWe developed a medium-throughput screening for drug repurposing against HMPV infection. C_LIO_LIEvaluation of a large drug library identified 5 candidates with low M to nM IC50 values against HMPV growth. C_LIO_LIThe approved drug mycophenolic acid (MPA) is a nM inhibitor of HMPV in vitro infection C_LIO_LIHuman MPA plasma levels upon oral dosing are 10x higher than MPA IC50 against HMPV in vitro infection. C_LI

pharmacology and toxicology↗