Structure and function analysis of a potent human neutralizing antibody CA521 against SARS-CoV-2
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… SARS-CoV-2 Spike protein transfected CHO cells (GenScript RD00819) were cultured for
two passages and then harvested, followed by washing twice with FACS buffer (0.2% BSA in
PBS). Totally, 1 × 10 5 CHO-SARS-CoV-2-Spike cells were stained with isotype control IgG or … |
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Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing COVID-19 pandemic, which has resulted in more than two million deaths at 2021 February . There is currently no approved therapeutics for treating COVID-19. The SARS-CoV-2 Spike protein is considered a key therapeutic target by many researchers. Here we describe the identification of several monoclonal antibodies that target SARS-CoV-2 Spike protein. One human antibody, CA521, demonstrated neutralization potential by immunizing human antibody transgenic mice. CA521 showed potent SARS-CoV-2-specific neutralization activity against SARS-CoV-2 pseudovirus and authentic SARS-CoV-2 infection in vitro. CA521 also demonst... More
Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is the causative agent of the ongoing COVID-19 pandemic, which has resulted in more than two million deaths at 2021 February . There is currently no approved therapeutics for treating COVID-19. The SARS-CoV-2 Spike protein is considered a key therapeutic target by many researchers. Here we describe the identification of several monoclonal antibodies that target SARS-CoV-2 Spike protein. One human antibody, CA521, demonstrated neutralization potential by immunizing human antibody transgenic mice. CA521 showed potent SARS-CoV-2-specific neutralization activity against SARS-CoV-2 pseudovirus and authentic SARS-CoV-2 infection in vitro. CA521 also demonstrated having a long half-life of 9.5 days in mice and 9.3 days in rhesus monkeys. CA521 inhibited SARS-CoV-2 infection in SARS-CoV-2 susceptible mice at a therapeutic setting with virus titer of the lung reduced by 4.5 logs. Structural analysis by cryo-EM revealed that CA521 recognizes an epitope overlapping with angiotensin converting enzyme 2 (ACE2)-binding sites in SARS-CoV-2 RBD in the Spike protein. CA521 blocks the interaction by binding all three RBDs of one SARS-CoV-2 spike trimer simultaneously. These results demonstrate the importance for antibody-based therapeutic interventions against COVID-19 and identifies CA521 a promising antibody that reacts with SARS-CoV-2 Spike protein to strongly neutralize its activity.
