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

ABSTRACT

Severe acute respiratory syndrome coronavirus (SARS-CoV-2) is responsible for the COVID-19 pandemic, causing health and economic problems. 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 membrane binds to the angiotensin converting enzyme 2 (ACE2) receptor 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 vitro and in vivo SARS-CoV-2 infection, better than ACE2-Ig. Mechanistically we show that anti-spike antibodies 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 concentration infection. 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.