![]() ![]() ![]() Following the RBD, S1 also contains two subdomains (SD1 and SD2) ( 7). Two major domains in coronavirus S1 have been identified, including an N-terminal domain (NTD) and a C-terminal domain (CTD) also called receptor-binding domain (RBD). The S protein ectodomain consists of a receptor-binding subunit S1 and a membrane-fusion subunit S2 ( 4, 7, 8). The S protein is a homotrimeric class I fusion protein that forms large protrusions from the virus surface and undergoes a substantial structural rearrangement to fuse the viral membrane with the host-cell membrane once it binds to a host-cell receptor ( 5, 6). As of 4 November 2020, there were no approved therapeutics or vaccines against SARS-CoV-2 and other human-infecting coronaviruses.Īs in other coronaviruses, the spike (S) glycoprotein of SARS-CoV-2 is a membrane-fusion machine that mediates receptor recognition and viral entry into cells and is the primary target of the humoral immune response during infection ( 3, 4). By 29 June 2020, there had been 9,962,193 laboratory-confirmed SARS-CoV-2 infections globally, leading to 498,723 deaths. The recent coronavirus disease 2019 (COVID-19) pandemic is caused by a novel coronavirus named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). In the past few decades, newly evolved coronaviruses have posed a global threat to public health, including outbreaks of the severe acute respiratory syndrome coronavirus (SARS-CoV) in 2002–2003 and the Middle East respiratory syndrome coronavirus (MERS-CoV) in 2012, which caused thousands of infections, and their mortality rates were about 10.0 and 34.4%, respectively ( 3). Our findings depict the mechanism of ACE2-induced S trimer conformational transitions from the ground prefusion state toward the postfusion state, facilitating development of anti–SARS-CoV-2 vaccines and therapeutics.Ĭoronaviruses are a family of large, enveloped, positive-stranded RNA viruses that cause upper respiratory, gastrointestinal, and central nervous system diseases in humans and other animals ( 1, 2). We defined the RBD T470-T478 loop and Y505 as viral determinants for specific recognition of SARS-CoV-2 RBD by ACE2. Notably, the SARS-CoV-2 S trimer appears much more sensitive to the ACE2 receptor than the SARS-CoV S trimer regarding receptor-triggered transformation from the closed prefusion state to the fusion-prone open state, potentially contributing to the superior infectivity of SARS-CoV-2. Accompanying ACE2 binding to the up receptor-binding domain (RBD), the associated ACE2-RBD exhibits continuous swing motions. We report the cryo-EM structures of a tightly closed SARS-CoV-2 S trimer with packed fusion peptide and an ACE2-bound S trimer at 2.7- and 3.8-Å resolution, respectively. The SARS-CoV-2 trimeric spike (S) glycoprotein interacts with the human ACE2 receptor to mediate viral entry into host cells. The recent outbreaks of SARS-CoV-2 pose a global health emergency. ![]()
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