新冠病毒S蛋白 z-bo 2020-10-30 793

　　The new coronavirus SARS-CoV-2 caused Coronavirus Disease (COVID-19) in 2019 and is currently rampant worldwide. There is an urgent need for an effective preventive vaccine to combat this virus. However, there is currently no human vaccine against SARS-CoV-2, but about 120 candidate vaccines are being developed. SARS-CoV-2 and two other closely related highly pathogenic viruses SARS-CoV and MERS-CoV belong to the β-coronavirus genus of the coronavirus family.

　　SARS-CoV-2 has a 30 kb single-stranded RNA genome. The nucleocapsid protein (N) and the outer membrane composed of membrane protein (M), envelope protein (E) and spike protein (S) cover the genome. Like SARS-CoV, the S protein of SARS-CoV-2 binds to the co-receptor angiotensin-converting enzyme 2 (ACE2) through the receptor binding domain (RBD) and mediates the virus to host cells. Do it. The S protein contains two functional subsystems, S1 and S2, in which S1 is involved in the binding of host cell receptors, and the S2 subunit is involved in the fusion of the viral membrane and the cell membrane. During the infection process, the S protein is cleaved into N-terminal S1 and C-terminal S2 subunits by host proteases (such as TMPRSS2), changing from the pre-fusion state to the post-fusion state. S1 and S2 are composed of an extracellular domain (ECD) and a single transmembrane helix, which mediate receptor binding and membrane fusion, respectively. S1 consists of an N-terminal domain (NTD) and a receptor binding domain (RBD), which are essential for determining the orientation of the tissue and host range.

　　"Analysis of the specificity and kinetic characteristics of neutralizing antibodies (nAbs) caused by SARS-CoV-2 infection is essential for understanding immune protection and determining vaccine design goals.

　　In a new study, researchers from the University of Washington and Humanbs Biomed SA, a subsidiary of Vir Biotechnology, found that SARS-CoV-2 peak protein and nucleoprotein (NP) antibody response strength and neutralizing antibody titers are all related to clinical scores . doing. The receptor binding domain (RBD) of SARS-CoV-2 spike protein has immunodominance and is also the target of 90% neutralizing antibodies in SARS-CoV-2 immune serum. The overall RBD-specific serum IgG titer decreases with the 49-day half-life, but the nAb titer and affinity increase with time in some individuals, which is consistent with affinity maturation. I'm. .. These researchers used monoclonal antibodies to structurally determine the RBD antigen map and serologically quantified serum antibodies against different RBD epitopes, thereby creating two main receptor binding motifs. The antigenic site has been identified. These findings explain the immunological advantages of the receptor-binding motif and guide the design of COVID-19 vaccines and drug development.