Antibody-mediated cell entry of SARS-CoV-2

Kibria, M. G.; Lavine, C. L.; Tang, W.; Wang, S.; Gao, H.; Shi, W.; Zhu, H.; Voyer, J.; Rits-Volloch, S.; Keerti, F.; Bi, C.; Peng, H.; Wesemann, D.; Lu, J.; Xie, H.; Seaman, M. S.; Chen, B.

doi:10.1101/2023.02.20.529249

bioRxiv · 10.1101/2023.02.20.529249

Antibody-mediated cell entry of SARS-CoV-2

Kibria, M. G.·Lavine, C. L.·Tang, W.·Wang, S.·Gao, H.·Shi, W.·Zhu, H.·Voyer, J.·Rits-Volloch, S.·Keerti, F.·Bi, C.·Peng, H.·Wesemann, D.·Lu, J.·Xie, H.·Seaman, M. S.·Chen, B.

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Abstract

Severe 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. We report here 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. 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 interactions with the spike protein are dispensable for SARS-CoV-2 entry. These results suggest that antibody responses against SARS-CoV-2 may expand the viral tropism to otherwise nonpermissive cell types; they have important implications for viral transmission and pathogenesis.

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Kibria, M. G., Lavine, C. L., Tang, W., Wang, S., Gao, H., Shi, W., Zhu, H., Voyer, J., Rits-Volloch, S., Keerti, F., Bi, C., Peng, H., Wesemann, D., Lu, J., Xie, H., Seaman, M. S., Chen, B.. 2023-02-20. Antibody-mediated cell entry of SARS-CoV-2. https://doi.org/10.1101/2023.02.20.529249

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