Neutralizing antibody is one of the most effective interventions for acute pathogenicinfection. Currently, over three million people have been identified for SARS-CoV-2infection but SARS-CoV-2-specific vaccines and neutralizing antibodies are stilllacking. SARS-CoV-2 infects host cells by interacting with angiotensin convertingenzyme-2 (ACE2) via the S1 receptor-binding domain (RBD) of its surface spikeglycoprotein. Therefore, blocking the interaction of SARS-CoV-2-RBD and ACE2 byantibody would cause a directly neutralizing effect against virus. In the current study,we selected the ACE2 interface of SARS-CoV-2-RBD as the targeting epitope forneutralizing antibody screening. We performed site-directed screening ... More
Neutralizing antibody is one of the most effective interventions for acute pathogenicinfection. Currently, over three million people have been identified for SARS-CoV-2infection but SARS-CoV-2-specific vaccines and neutralizing antibodies are stilllacking. SARS-CoV-2 infects host cells by interacting with angiotensin convertingenzyme-2 (ACE2) via the S1 receptor-binding domain (RBD) of its surface spikeglycoprotein. Therefore, blocking the interaction of SARS-CoV-2-RBD and ACE2 byantibody would cause a directly neutralizing effect against virus. In the current study,we selected the ACE2 interface of SARS-CoV-2-RBD as the targeting epitope forneutralizing antibody screening. We performed site-directed screening by phage displayand finally obtained one IgG antibody (4A3) and several domain antibodies. Amongthem, 4A3 and three domain antibodies (4A12, 4D5, and 4A10) were identified to actas neutralizing antibodies due to their capabilities to block the interaction betweenSARS-CoV-2-RBD and ACE2-positive cells. he domain antibody 4A12 was predictedto have the best accessibility to all three ACE2-interfaces on the spike homotrimer.Pseudovirus and authentic SARS-CoV-2 neutralization assays showed that all fourantibodies could potently protect host cells from virus infection. Overall, we isolatedmultiple formats of SARS-CoV-2-neutralizing antibodies via site-directed antibodyscreening, which could be promising candidate drugs for the prevention and treatmentof COVID-19.
