Novel Wide‐Spectrum Virucidal Lipid Nanoparticles

Abstract Viral infections remain a global health challenge, highlighting the urgent need for innovative antiviral strategies. Broad‐spectrum antivirals offer a promising solution. Virustatic compounds fail due to their reversible mechanisms, while existing virucidal agents are frequently limited by toxicity. Here, POSTAN, a novel, biocompatible virucidal lipid nanoparticle engineered for direct antiviral activity is presented. Composed of polyoxyethylene sorbitan oleate (PO) and sodium taurodeoxycholate (ST), POSTAN mimics heparan sulfate (HS) proteoglycans and lipid rafts—host cell structures commonly exploited by viruses for attachment. POSTAN demonstrates optimal physicochemical properties for pulmonary delivery, minimal to no toxicity in Vero cells and human airway epithelial (HAE) cultures, and a favorable safety profile in neonatal mice. It exhibits broad‐spectrum virucidal activity at micromolar concentrations against herpes simplex virus (HSV), respiratory syncytial virus (RSV), Zika virus, Chikungunya virus (CHIKV), and SARS‐CoV‐2 by disrupting viral envelopes. In HAE cultures, POSTAN reduced SARS‐CoV‐2 titers by 5‐ and 3‐log before and after infection. In a neonatal RSV mouse model, intranasal POSTAN led to 6‐, 10‐, and 19‐fold reductions in lung viral titers following prophylactic, therapeutic, or combined prophylactic and therapeutic treatments. It mitigated lung pathology and prevented hemorrhage. These findings support POSTAN as a safe, effective, broad‐spectrum antiviral platform for respiratory infections.