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Structure of SARS-CoV-2 XBB.1.5 spike RBD in complex with ACE2
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 PubMedCirculation of SARS-CoV-2 Omicron XBB has resulted in the emergence of XBB.1.5, a new Variant of Interest. Our phylogenetic analysis suggests that XBB.1.5 evolved from XBB.1 by acquiring the S486P spike (S) mutation, subsequent to the acquisition of a nonsense mutation in ORF8. Neutralization assays showed similar abilities of immune escape between XBB.1.5 and XBB.1. We determine the structural basis for the interaction between human ACE2 and the S protein of XBB.1.5, showing similar overall structures between the S proteins of XBB.1 and XBB.1.5. We provide the intrinsic pathogenicity of XBB.1 and XBB.1.5 in hamsters. Importantly, we find that the ORF8 nonsense mutation of XBB.1.5 resulted in impairment of MHC suppression. In vivo experiments using recombinant viruses reveal that the XBB.1.5 mutations are involved with reduced virulence of XBB.1.5. Together, our study identifies the two viral functions defined the difference between XBB.1 and XBB.1.5. Virological characteristics of the SARS-CoV-2 Omicron XBB.1.5 variant.,Tamura T, Irie T, Deguchi S, Yajima H, Tsuda M, Nasser H, Mizuma K, Plianchaisuk A, Suzuki S, Uriu K, Begum MM, Shimizu R, Jonathan M, Suzuki R, Kondo T, Ito H, Kamiyama A, Yoshimatsu K, Shofa M, Hashimoto R, Anraku Y, Kimura KT, Kita S, Sasaki J, Sasaki-Tabata K, Maenaka K, Nao N, Wang L, Oda Y, Ikeda T, Saito A, Matsuno K, Ito J, Tanaka S, Sato K, Hashiguchi T, Takayama K, Fukuhara T Nat Commun. 2024 Feb 8;15(1):1176. doi: 10.1038/s41467-024-45274-3. PMID:38332154[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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