SARS-CoV-2 receptor binding domain fusion protein efficiently neutralizes virus infection

Abigael Eva Chaouat, Hagit Achdout, Inbal Kol, Orit Berhani, Gil Roi, Einat B. Vitner, Sharon Melamed, Boaz Politi, Eran Zahavy, Ilija Brizic, Tihana Lenac Rovis, Or Alfi, Dana Wolf, Stipan Jonjic, Tomer Israely, Ofer Mandelboim*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

16 Scopus citations


Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is responsible for the COVID-19 pandemic. Currently, as dangerous mutations emerge, there is an increased demand for specific treatments for SARS-CoV-2 infected patients. The spike glycoprotein on the virus envelope binds to the angiotensin converting enzyme 2 (ACE2) on host cells through its receptor binding domain (RBD) to mediate virus entry. Thus, blocking this interaction may inhibit viral entry and consequently stop infection. Here, we generated fusion proteins composed of the extracellular portions of ACE2 and RBD fused to the Fc portion of human IgG1 (ACE2-Ig and RBD-Ig, respectively). We demonstrate that ACE2-Ig is enzymatically active and that it can be recognized by the SARS-CoV-2 RBD, independently of its enzymatic activity. We further show that RBD-Ig efficiently inhibits in-vivo SARS-CoV-2 infection better than ACE2-Ig. Mechanistically, we show that anti-spike antibody generation, ACE2 enzymatic activity, and ACE2 surface expression were not affected by RBD-Ig. Finally, we show that RBD-Ig is more efficient than ACE2-Ig at neutralizing high virus titers. We thus propose that RBD-Ig physically blocks virus infection by binding to ACE2 and that RBD-Ig should be used for the treatment of SARS-CoV-2-infected patients.

Original languageAmerican English
Article numbere1010175
JournalPLoS Pathogens
Issue number12
StatePublished - Dec 2021

Bibliographical note

Publisher Copyright:
© 2021 Chaouat et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.


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