A Broad‐Spectrum Antiviral Phase‐Transformable Liposome with Membrane Fusion‐Mediated Virucidal Capability

Abstract Viral infection is a significant threat to global public health. Available antiviral drugs are effective only for specific viruses. It is imperative to develop broad‐spectrum antiviral drugs. The heparin sulfate proteoglycan (HSPG) biomimetic strategy holds great promise to design broad‐spectrum antiviral materials. However, the reversible binding of HSPG‐mimicking nanoparticles with virions presents a potential risk of reinfection. Herein, a sulfonated liposome (SC_Lip) that can trigger phase transition below pH 6.5 is screened to combat viral infection at all stages. SC_Lip can realize pH‐induced phase transition, which triggers membrane fusion with viral envelope and subsequent viral inactivation. Therefore, SC_Lip exhibits virucidal activity via membrane fusion with viral envelope in both acidic viral infection microenvironment and intracellular acidic lysosomes. The broad‐spectrum virucidal activity of SC_Lip is confirmed by different types of viruses, including coronavirus (SARS‐CoV‐2), retrovirus (LV), and herpesvirus (HSV‐1). The in vivo antiviral effect of SC_Lip is further verified by a rat HSV‐1 anterior uveitis model. Overall, SC_Lip with broad‐spectrum virucidal ability holds great promise to fight against emerging viral pandemics in the future.