Neutralizing antibodies targeting the SARS?CoV?2 receptor binding domain isolated from a naïve human antibody library

Infection with SARS-CoV-2 elicits robust antibody responses in some patients, a majority of the response directed at receptor binding domain (RBD) spike surface glycoprotein. Remarkably, many patient-derived antibodies that potently inhibit viral infection harbor few to no mutations from germline, suggesting naïve libraries are viable means for discovery novel neutralizing antibodies. Here, we used yeast surface-display library human isolate and characterize three target RBD: one blocks interaction angiotensin-converting enzyme 2 (ACE2), SARS-CoV-2, two other epitopes on RBD. These neutralized spike-pseudotyped lentivirus IC50 values as low 60 ng/ml vitro. Using biolayer interferometry-based competition assay, determined these have distinct but overlapping elicited during natural COVID-19 infection. Taken together, analyses highlight how vitro selection can mimic humoral vivo, yielding various be effectively targeted