Open AccessSARS-CoV-2 receptor binding domain fusion protein efficiently neutralizes virus infection
Author(s) -
Abigael Eva Chaouat,
Hagit Achdout,
Inbal Kol,
Orit Berhani,
Gil Roi,
Einat B. Vitner,
Sharon Melamed,
Boaz Politi,
Eran Zahavy,
Ilija Brizić,
Tihana Lenac Roviš,
Or Alfi,
Dana Wolf,
Stipan Jonjić,
Tomer Israely,
Ofer Mandelboim
Publication year - 2021
Publication title -
plos pathogens
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.719
H-Index - 206
eISSN - 1553-7374
pISSN - 1553-7366
DOI - 10.1371/journal.ppat.1010175
Subject(s) - virus , virology , viral entry , glycoprotein , antibody , biology , coronavirus , neutralizing antibody , receptor , vero cell , fusion protein , antibody dependent enhancement , enzyme , viral envelope , recombinant dna , microbiology and biotechnology , viral replication , covid-19 , immunology , biochemistry , gene , medicine , disease , pathology , infectious disease (medical specialty)
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.