The evolution of coronaviruses, such as SARS-CoV-2, makes broad-spectrum coronavirus preventional or therapeutical strategies highly sought after. Here we report a human angiotensin-converting enzyme 2 (ACE2)-targeting monoclonal antibody, 3E8, blocked the S1-subunits and pseudo-typed virus constructs from multiple coronaviruses including SARS-CoV-2, SARS-CoV-2 mutant variants (SARS-CoV-2-D614G, B.1.1.7, B.1.351, B.1.617.1, and P.1), SARS-CoV and HCoV-NL63, without markedly affecting the physiological activities of ACE2 or causing severe toxicity in ACE2 “knock-in” mice. 3E8 also blocked live SARS-CoV-2 infection in vitro and in a prophylactic mouse model of COVID-19. Cryo-EM and “alanine walk” studies revealed the key binding residues on ACE2 interacting with the CDR3 domain of 3E8 heavy chain. Although full evaluation of safety in non-human primates is necessary before clinical development of 3E8, we provided a potentially potent and “broad-spectrum” management strategy against all coronaviruses that utilize ACE2 as entry receptors and disclosed an anti-coronavirus epitope on human ACE2.
【저자키워드】 Infectious diseases, Drug development, 【초록키워드】 COVID-19, Evolution, SARS-CoV-2, ACE2, Coronaviruses, coronavirus, SARS-CoV, B.1.351, SARS-COV-2 infection, monoclonal antibody, variant, Infection, Toxicity, in vitro, Prophylactic, virus, human ACE2, B.1.1.7, mice, non-human primates, P.1, B.1.617.1, management, HCoV, D614G, cryo-EM, mutant, non-human primate, epitope, binding, HCoV-NL63, angiotensin, heavy chain, physiological activities, residue, domain, human Angiotensin-converting enzyme, Alanine, clinical development, live SARS-CoV-2, entry receptor, multiple coronaviruses, cryo, CDR3, blocked, provided, coronavirus, affecting, multiple coronaviruses, physiological activity,