The outbreak of COVID-19 caused by SARS-CoV-2 has widely spread worldwide as continuous global public threats. To better control the pandemics, anti-SARS-CoV-2 drugs and vaccines are urgently to be developed. SARS-CoV-2 has four main structural proteins, namely S, M, N, E. S protein is responsible for binding to cellular receptors and prompting membrane fusion for virus entry to target cells. ACE2 is reported as the receptor of SARS-CoV-2, while the host cell serine protease TMPRSS2 primes the S protein of SARS-CoV-2 for entry. Because of the key functions, S protein is the main target for antibody-mediated neutralization and the focus of vaccine development.

Neutralization assays determine the ability of an antibody to inhibit virus infection of cultured cells and the resulting cytopathic effects of viral replication, which are important for drug discovery and vaccine development. Virus neutralization is a specialized type of immunoassay since it detects antibody that can block virus replication. Neutralizing antibodies generally recognize proteins or glycoproteins on the virus surface. There are several mechanisms for antibody neutralization including blocking attachment to the host cell, inhibiting penetration of the host cell membrane, or interfering with uncoating of the virus within the cell.