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Structure of the SARS-CoV-2 XBB.1 spike glycoprotein (closed-1 state)Structure of the SARS-CoV-2 XBB.1 spike glycoprotein (closed-1 state)
Structural highlights
FunctionSPIKE_SARS2 attaches the virion to the cell membrane by interacting with host receptor, initiating the infection (By similarity). Binding to human ACE2 receptor and internalization of the virus into the endosomes of the host cell induces conformational changes in the Spike glycoprotein (PubMed:32142651, PubMed:32075877, PubMed:32155444). Uses also human TMPRSS2 for priming in human lung cells which is an essential step for viral entry (PubMed:32142651). Proteolysis by cathepsin CTSL may unmask the fusion peptide of S2 and activate membranes fusion within endosomes.[HAMAP-Rule:MF_04099][1] [2] [3] mediates fusion of the virion and cellular membranes by acting as a class I viral fusion protein. Under the current model, the protein has at least three conformational states: pre-fusion native state, pre-hairpin intermediate state, and post-fusion hairpin state. During viral and target cell membrane fusion, the coiled coil regions (heptad repeats) assume a trimer-of-hairpins structure, positioning the fusion peptide in close proximity to the C-terminal region of the ectodomain. The formation of this structure appears to drive apposition and subsequent fusion of viral and target cell membranes.[HAMAP-Rule:MF_04099] Acts as a viral fusion peptide which is unmasked following S2 cleavage occurring upon virus endocytosis.[HAMAP-Rule:MF_04099] Publication Abstract from PubMedIn late 2022, SARS-CoV-2 Omicron subvariants have become highly diversified, and XBB is spreading rapidly around the world. Our phylogenetic analyses suggested that XBB emerged through the recombination of two cocirculating BA.2 lineages, BJ.1 and BM.1.1.1 (a progeny of BA.2.75), during the summer of 2022. XBB.1 is the variant most profoundly resistant to BA.2/5 breakthrough infection sera to date and is more fusogenic than BA.2.75. The recombination breakpoint is located in the receptor-binding domain of spike, and each region of the recombinant spike confers immune evasion and increases fusogenicity. We further provide the structural basis for the interaction between XBB.1 spike and human ACE2. Finally, the intrinsic pathogenicity of XBB.1 in male hamsters is comparable to or even lower than that of BA.2.75. Our multiscale investigation provides evidence suggesting that XBB is the first observed SARS-CoV-2 variant to increase its fitness through recombination rather than substitutions. Virological characteristics of the SARS-CoV-2 XBB variant derived from recombination of two Omicron subvariants.,Tamura T, Ito J, Uriu K, Zahradnik J, Kida I, Anraku Y, Nasser H, Shofa M, Oda Y, Lytras S, Nao N, Itakura Y, Deguchi S, Suzuki R, Wang L, Begum MM, Kita S, Yajima H, Sasaki J, Sasaki-Tabata K, Shimizu R, Tsuda M, Kosugi Y, Fujita S, Pan L, Sauter D, Yoshimatsu K, Suzuki S, Asakura H, Nagashima M, Sadamasu K, Yoshimura K, Yamamoto Y, Nagamoto T, Schreiber G, Maenaka K, Hashiguchi T, Ikeda T, Fukuhara T, Saito A, Tanaka S, Matsuno K, Takayama K, Sato K Nat Commun. 2023 May 16;14(1):2800. doi: 10.1038/s41467-023-38435-3. PMID:37193706[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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