Abstract To circumvent the devastating pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) infection, a humanized decoy antibody (ACE2‐Fc fusion protein) was designed to target the interaction between viral spike protein and its cellular receptor, angiotensin‐converting enzyme 2 (ACE2). First, we demonstrated that ACE2‐Fc could specifically abrogate virus replication by blocking the entry of SARS‐CoV‐2 spike‐expressing pseudotyped virus into both ACE2‐expressing lung cells and lung organoids. The impairment of viral entry was not affected by virus variants, since efficient inhibition was also observed in six SARS‐CoV‐2 clinical strains, including the D614G variants which have been shown to exhibit increased infectivity. The preservation of peptidase activity also enables ACE2‐Fc to reduce the angiotensin II‐mediated cytokine cascade. Furthermore, this Fc domain of ACE2‐Fc was shown to activate NK cell degranulation after co‐incubation with Spike‐expressing H1975 cells. These promising characteristics potentiate the therapeutic prospects of ACE2‐Fc as an effective treatment for COVID‐19. Currently, there is no effective strategy to fight against the COVID‐19 pandemic. We aim to design and develop a humanized decoy antibody to block SARS‐CoV‐2 infection.
【저자키워드】 immunology, COVID‐19, SARS‐CoV‐2, Microbiology, Virology & Host Pathogen Interaction, virus infection, ACE2‐Fc, decoy antibody, 【초록키워드】 Treatment, ACE2, coronavirus, pandemic, antibody, Infection, NK cell, cytokine, severe acute respiratory syndrome Coronavirus, viral entry, Spike protein, COVID‐19, SARS‐CoV‐2, Viral, Characteristics, Pseudotyped virus, cells, D614G variant, therapeutic, virus replication, lung organoids, virus variants, fusion protein, respiratory, Strains, preservation, Angiotensin II, Interaction, angiotensin, viral spike protein, acute respiratory syndrome, acute respiratory syndrome coronavirus, acute respiratory syndrome coronavirus 2, enzyme, domain, peptidase, SARS‐CoV‐2 infection, D614G variants, SARS‐CoV‐2 spike, cascade, impairment, lung cells, cellular receptor, degranulation, humanized, effective, lung cell, shown, develop, caused, demonstrated, abrogate, activate, reduce, not affected, circumvent, H1975, 【제목키워드】 antibody, COVID‐19, Viral, block, Prevent,