Broad Neutralizing Antibodies Against SARS-CoV-2: Current Progress and Engineering Strategies

The high-frequency mutation characteristics of SARS-CoV-2 have posed formidable challenges to the development of vaccines and therapeutic agents. Neutralizing antibodies, which serve as effective tools for prevention and control, have undergone continuous updates and iterations in response to viral mutations. This article provides a comprehensive review of researchers’ efforts to achieve both high neutralizing potency and high mutation tolerance in SARS-CoV-2–targeting neutralizing antibodies. Building on the characteristics of conventional antibodies directed against distinct epitopes on the S protein, it further discusses the research on nanobodies, antibody cocktails, multi-specific antibodies, and other antibody formats and engineering approaches, including artificial intelligence–enabled optimization. Each antibody-based strategy targeting SARS-CoV-2 has its own distinctive advantages and potential applications, providing an integrated perspective to support the continued development of antiviral neutralizing antibodies.