Abstract
Excessive inflammatory responses contribute to the pathogenesis and lethality of highly pathogenic human coronaviruses, but the underlying mechanism remains unclear. In this study, the N proteins of highly pathogenic human coronaviruses, including severe acute respiratory syndrome coronavirus (SARS-CoV), middle east respiratory syndrome coronavirus (MERS-CoV) and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), were found to bind MASP-2, a key serine protease in the lectin pathway of complement activation, resulting in excessive complement activation by potentiating MBL-dependent MASP-2 activation, and the deposition of MASP-2, C4b, activated C3 and C5b-9. Aggravated inflammatory lung injury was observed in mice infected with adenovirus expressing the N protein. Complement hyperactivation was also observed in SARS-CoV-2-infected patients. Either blocking the N protein:MASP-2 interaction, MASP-2 depletion or suppressing complement activation can significantly alleviate N protein-induced complement hyperactivation and lung injury in vitro and in vivo. Altogether, these data suggested that complement suppression may represent a novel therapeutic approach for pneumonia induced by these highly pathogenic coronaviruses.
【초록키워드】 SARS-CoV-2, Coronaviruses, coronavirus, Pathogenesis, Pneumonia, SARS-CoV, complement, Lung injury, in vitro, MERS-CoV, Adenovirus, mice, in vivo, mechanism, lectin pathway, human coronaviruses, MASP-2, Interaction, Inflammatory response, Therapeutic approach, acute respiratory syndrome, Activation, These data, serine protease, respiratory syndrome coronavirus, SARS-CoV-2-infected patients, Hyperactivation, highly pathogenic, inflammatory lung injury, resulting, significantly, activated, contribute, suggested, expressing, alleviate, the N protein, Aggravated, 【제목키워드】 Inflammation, N protein, Complement pathway, pathogenic coronavirus, aggravate,