
Neutralization of SARS-CoV-2 infection by antibodies targeting diverse epitopes
The COVID-19 pandemic that started in late 2019 is sweeping through the world, posing historic challenges to global health, and disrupting social and economic lives. Previous and recent studies indicate that monoclonal antibodies can be efficacious in preventing and treating SARS-CoV-1 and SARS-CoV-2 infections. Using a phage display platform, we have identified dozens of monoclonal antibodies that bind to diverse epitope groups on the SARS-CoV-2 spike protein. Many of them bound to the receptor binding domain (RBD) and inhibited ACE2-RBD interaction. Several of them were capable of inhibiting SARS-CoV-2 spike protein pseudo-typed virus (pseudovirus) entry. In addition, we isolated a dozen of S2 binding antibodies that prevented pseudovirus entry without inhibiting the ACE2-RBD interaction. A bi-epitopic antibody constructed from two non-competing, RBD binding, neutralizing antibodies displayed higher potency than either of them alone. Combinations of RBD and S2 binding antibodies displayed additive inhibitory effects against pseudovirus infection. The new antibodies and strategies reported here could expand the arsenal of anti-COVID-19 therapeutics and help understand the viral entry mechanism, the pathogenesis of the SARS-CoV-2, and anti-SARS-CoV-2 vaccine development.