Plant MIR2911 in honeysuckle is effective against SARS-CoV-2 variant.

The COVID-19 pandemic remains a global health challenge, with the emergence of new SARS-CoV-2 variants complicating treatment and prevention efforts. MIR2911, a plant-derived microRNA from honeysuckle, has shown antiviral activity against the original strain of SARS-CoV-2. Here, we investigate its efficacy against the Delta variant (B.1.617.2). Computational analysis using RNAhybrid identified multiple MIR2911 recognition elements (MREs) in the Delta variant genome. Reporter assays confirmed that MIR2911 binds these MREs, significantly reducing luciferase activity. In Vero E6 cells infected with the Delta variant, MIR2911 suppressed RdRP RNA expression and viral replication in a dose-dependent manner, as evidenced by plaque assays. To enhance its therapeutic potential, we developed a novel delivery system using JCPyV CLP, a virus-like particle capable of transducing genetic material. CLP-mediated delivery of MIR2911 not only further improved its antiviral efficacy, reducing RdRP RNA expression and viral plaque formation with minimal toxicity, but also significantly enhanced MIR2911 transfection efficiency compared to conventional liposome-based methods. These findings highlight the potential of MIR2911, delivered via JCPyV CLP, as a promising therapeutic strategy for combating SARS-CoV-2 replication, including the highly virulent Delta variant.