摘要:SummaryThe different variants of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) have attracted most public concern because they caused “wave and wave” COVID-19 pandemic. The initial step of viral infection is mediated by the SARS-CoV-2 Spike (S) protein, which mediates the receptor recognition and membrane fusion between virus and host cells. Neutralizing antibodies (nAbs) targeting the S protein of SARS-CoV-2 have become promising candidates for clinical intervention strategy, while multiple studies have shown that different variants have enhanced infectivity and antibody resistance. Here, we explore the structure and function of STS165, a broadly inter-Spike bivalent nAb against SARS-CoV-2 variants and even SARS-CoV, contributing to further understanding of the working mechanism of nAbs.Graphical abstractDisplay OmittedHighlights•STS165 broadly neutralizes different variants of SARS-CoV-2 and even SARS-CoV•STS165 exhibits inter-Spike bivalent binding characteristics•STS165 may work as an ideal partner to form therapeutic antibody cocktailsBiochemistry applications; Molecular Structure; Structural biology; Virology