Inhalation of substances, including viral particles, the RNA virus capsid (S) glycoprotein binds the cellular receptor angiotensin-converting enzyme 2 (ACE2) and mediates fusion of the viral and cellular membranes through a pre- to postfusion conformation transition. The AOP report the S glycoprotein of viral capsid in complex with its host cell receptor ACE2 resulted in acute respiratory distress associated mortality by enhanced inflammation in pulmonary tissue.
The ACE2 gene encodes the angiotensin-converting enzyme-2, which has been proved to be the receptor for both the SARS-coronavirus (SARS-CoV) and the human respiratory coronavirus. The higher levels of receptor expression achieved by expression of recombinant ACE2 could be relevant for cell–cell fusion. The underlying mechanisms remain to be elucidated and could play a role in the entry of cell-free virus into cells and finally acute respiratory distress associated mortality .
This AOP not only contributes new tools to study entry of the viral particles into cells and localize its receptor-binding domain of ACE2 but also could serve in the development of novel vaccine immunogens and therapeutics for prevention and treatment of RNA virus.
Kuba K, Imai Y, Rao S, Gao H, Guo F, Guan B, Huan Y, Yang P, Zhang Y, Deng W, Bao L, Zhang B, Liu G, Wang Z, Chappell M, Liu Y, Zheng D, Leibbrandt A, Wada T, Slutsky AS, Liu D, Qin C, Jiang C, Penninger JM (Aug 2005). "A crucial role of angiotensin converting enzyme 2 (ACE2) in SARS coronavirus-induced lung injury". Nature Medicine. 11 (8): 875–9. doi:10.1038/nm1267. PMID16007097.
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