Antibody‐mediated SARS‐CoV‐2 entry in cultured cells

Abstract

AbstractSevere acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) enters host cells by first engaging its cellular receptor angiotensin converting enzyme 2 (ACE2) to induce conformational changes in the virus‐encoded spike protein and fusion between the viral and target cell membranes. Here, we report that certain monoclonal neutralizing antibodies against distinct epitopic regions of the receptor‐binding domain of the spike can replace ACE2 to serve as a receptor and efficiently support membrane fusion and viral infectivity in vitro. These receptor‐like antibodies can function in the form of a complex of their soluble immunoglobulin G with Fc‐gamma receptor I, a chimera of their antigen‐binding fragment with the transmembrane domain of ACE2 or a membrane‐bound B cell receptor, indicating that ACE2 and its specific interaction with the spike protein are dispensable for SARS‐CoV‐2 entry. These results suggest that antibody responses against SARS‐CoV‐2 may help expand the viral tropism to otherwise nonpermissive cell types with potential implications for viral transmission and pathogenesis.