Mineralo-organic particles inhibit influenza A virus infection by targeting viral hemagglutinin activity

<b>Aim:</b> Mineralo-organic particles, naturally present in human body fluids, participate in ectopic calcification and inflammatory diseases. These particles coexist with influenza A virus (IAV) in the same microenvironment during viral infection. Our objective was to investigate the functional consequences of the potential interactions between these particles and the virions. <b>Materials &amp; methods:</b> We used <i>in vitro</i> models, including electron microscopy, fluorescence microscopy, hemagglutination assay and viral infection assays to examine the interactions. <b>Results:</b> Mineralo-organic particles bind to IAV virions through interactions involving particle-bound fetuin-A and mineral content, effectively engaging viral hemagglutinin. These interactions result in hindered viral infection. <b>Conclusion:</b> These findings uncover the novel interactions between mineralo-organic particles and IAV, highlighting the impact of virus microenvironment complexity. <i>In vitro</i> mineralo-organic particles, produced in controlled settings, enabled study of particle−virion interactions with physiological implications. These particles are capable of binding to influenza A virus and reduce infection in mammalian cells. Mineralo-organic particles exhibit the ability to inhibit influenza A virus-induced hemagglutination and disrupt viral attachment to cells by engaging in interactions between particle-associated fetuin-A and viral HA. Mineralo-organic particles are capable of engaging with virions, thereby presenting a particle-mediated host factor that influences infectious disease outcomes.