8r8k
From Proteopedia
XBB-4 Fab in complex with SARS-CoV-2 BA.2.12.1 Spike Glycoprotein
Structural highlights
FunctionA0A7L9WCR1_SARS2 Spike protein S1: attaches the virion to the cell membrane by interacting with host receptor, initiating the infection.[HAMAP-Rule:MF_04099] Spike protein S2': Acts as a viral fusion peptide which is unmasked following S2 cleavage occurring upon virus endocytosis.[HAMAP-Rule:MF_04099] Spike protein S2: 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] Publication Abstract from PubMedBA.2.86, a recently described sublineage of SARS-CoV-2 Omicron, contains many mutations in the spike gene. It appears to have originated from BA.2 and is distinct from the XBB variants responsible for many infections in 2023. The global spread and plethora of mutations in BA.2.86 has caused concern that it may possess greater immune-evasive potential, leading to a new wave of infection. Here, we examine the ability of BA.2.86 to evade the antibody response to infection using a panel of vaccinated or naturally infected sera and find that it shows marginally less immune evasion than XBB.1.5. We locate BA.2.86 in the antigenic landscape of recent variants and look at its ability to escape panels of potent monoclonal antibodies generated against contemporary SARS-CoV-2 infections. We demonstrate, and provide a structural explanation for, increased affinity of BA.2.86 to ACE2, which may increase transmissibility. A structure-function analysis shows SARS-CoV-2 BA.2.86 balances antibody escape and ACE2 affinity.,Liu C, Zhou D, Dijokaite-Guraliuc A, Supasa P, Duyvesteyn HME, Ginn HM, Selvaraj M, Mentzer AJ, Das R, de Silva TI, Ritter TG, Plowright M, Newman TAH, Stafford L, Kronsteiner B, Temperton N, Lui Y, Fellermeyer M, Goulder P, Klenerman P, Dunachie SJ, Barton MI, Kutuzov MA, Dushek O, Fry EE, Mongkolsapaya J, Ren J, Stuart DI, Screaton GR Cell Rep Med. 2024 May 21;5(5):101553. doi: 10.1016/j.xcrm.2024.101553. Epub 2024 , May 8. PMID:38723626[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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