Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation

Abstract

Fig. 4. Antigenicity of the 2019-nCoV RBD. (A) SARS-CoV RBD shown as a white molecular surface (PDB ID: 2AJF), with residues that vary in the 2019-nCoV RBD colored red. The ACE2-binding site is outlined with a black dashed line. (B) Biolayer interferometry sensorgram showing binding to ACE2 by the 2019-nCoV RBD-SD1. Binding data are shown as a black line, and the best fit of the data to a 1:1 binding model is shown in red.(C) Biolayer interferometry to measure cross-reactivity of the SARS-CoV RBD-directed antibodies S230, m396, and 80R. Sensor tips with immobilized antibodies were dipped into wells containing 2019-nCoV RBD-SD1, and the resulting data are shown as a black line.

The deadly coronaviruses: The 2003 SARS pandemic and the 2020 novel coronavirus epidemic in China

“…This rejects the hypothesis of emergence as a result of a recombination event [94,96]. Even though there are high similarities between SARS-CoV-2 S and RaTG13 S, there are two distinct differences: one is an "RRAR" furin recognition site formed by an insertion residues in the S1/S2 protease cleavage site in SARS-CoV-2, rather than the single Arginine in SARS-CoV [97][98][99][100][101]; the other difference is the presence of 29 variant residues between SARS-CoV-2 S and RaTG13 S, 17 of which mapped to the receptor binding domain (RBD) [97]. The identities of 5′-and 3′-UTR sequences are more than 83.6% consistent between SARS-CoV-2 and other β-CoVs, such as SARS-CoV [102].…”

Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein

“…This resemblance is further strengthened by our finding that SARS-CoV S elicited polyclonal Ab responses, potently neutralizing SARS-CoV-2 S-mediated entry into cells. We surmise most of these Abs target the highly conserved S 2 subunit (including the fusion peptide region) based on its structural similarity across SARS-CoV-2 and SARS-CoV, the lack of cross-reactivity of several S B -directed Abs (Tian et al, 2020;Wrapp et al, 2020), and previous reports showing that sera from SARS-CoV-infected individuals target this region (Zhang et al, 2004). We note that most SARS-CoV neutralizing Abs isolated to date target the S B domain and that several of them recognize the RBM and prevent receptor engagement (Hwang et al, 2006;Rockx et al, 2008;Rockx et al, 2010;Traggiai et al, 2004;Walls et al, 2019).…”

“…Approximately half of the particle images selected correspond to trimers harboring a single S B domain opened whereas the remaining half was accounted for by closed trimers with the three S B domains closed. A recently determined SARS-CoV-2 S structure also detected trimers with a single S B domain opened but none entirely closed(Wrapp et al, 2020). The observed conformational variability of S…”

Review of the 2019 novel coronavirus (SARS-CoV-2) based on current evidence

“…Coronavirus mainly recognizes the corresponding receptor on the target cell through the S protein on its surface and enters into the cell, then causing the occurrence of infection. A structure model analysis shows that SARS-CoV-2 binds ACE2 with above 10 folds higher affinity than SARS-CoV, but higher than the threshold required for virus infection [9]. The detailed mechanism about whether the SARS-CoV-2 would infect humans via binding of S-protein to ACE2, how strong the interaction is for risk of human transmission, and how SARS-CoV-2 causes pathological mechanisms of organs damage remains unknown, which need more studies to elaborate.…”