biostudies-literatureHwang JKorea Research Institute of Bioscience & Biotechnology (KRIBB) Research Initiative ProgramKorea Health Technology R&D Project through the Korea Health Industry Development Institute (KHIDI), funded by the Ministry of Health & Welfare, Republic of KoreaNational Research Foundation of Korea (NRF) grant funded by the Korea government (MSIT)44https://www.ebi.ac.uk/biostudies/studies/S-EPMC11761773biostudies-literatureUnknown23(1)Passive antibody therapies, typically administered via parenteral routes, have played a crucial role in the initial response to the COVID-19 pandemic. However, the ongoing evolution of SARS-CoV-2 has revealed significant limitations of this approach, primarily due to mutational escape and the inadequate delivery of antibodies to the upper respiratory tract. To overcome these challenges, we propose a novel prophylactic strategy involving the intranasal delivery of an antibody in combination with an Fc-binding nanodisc. This nanodisc, engineered to specifically bind to the Fc regions of IgG antibodies, served two key functions: extending the antibody's half-life in the larynx and trachea, and enhancing its neutralization efficacy. Notably, Sotrovimab, an FDA-approved monoclonal antibody thatJournal of nanobiotechnologyFc-binding nanodisc restores antiviral efficacy of antibodies with reduced neutralizing effects against evolving SARS-CoV-2 variants.PMC11761773KGM99424212020R1A2C2101964HI23C0392Son SYu SKim KWKweon DHYoon JHJung STHwang JKim BKChoo HChoi SKim SPark WJung SSong MSKim SJfalseFc-binding nanodisc restores antiviral efficacy of antibodies with reduced neutralizing effects against evolving SARS-CoV-2 variants.Passive antibody therapies, typically administered via parenteral routes, have played a crucial role in the initial response to the COVID-19 pandemic. However, the ongoing evolution of SARS-CoV-2 has revealed significant limitations of this approach, primarily due to mutational escape and the inadequate delivery of antibodies to the upper respiratory tract. To overcome these challenges, we propose a novel prophylactic strategy involving the intranasal delivery of an antibody in combination with an Fc-binding nanodisc. This nanodisc, engineered to specifically bind to the Fc regions of IgG antibodies, served two key functions: extending the antibody's half-life in the larynx and trachea, and enhancing its neutralization efficacy. Notably, Sotrovimab, an FDA-approved monoclonal antibody that2025-01-01T00:00:00Z2025 Jan2025-04-03T23:23:40.442Z2025-04-03T23:23:40.442ZS-EPMC117617733985674610.1186/s12951-025-03100-y