8err
From Proteopedia
SARS-CoV-2 Omicron BA.1 spike ectodomain trimer in complex with the S2X324 neutralizing antibody Fab fragment
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 PubMedSevere acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Omicron sublineages carry distinct spike mutations resulting in escape from antibodies induced by previous infection or vaccination. We show that hybrid immunity or vaccine boosters elicit plasma-neutralizing antibodies against Omicron BA.1, BA.2, BA.2.12.1, and BA.4/5, and that breakthrough infections, but not vaccination alone, induce neutralizing antibodies in the nasal mucosa. Consistent with immunological imprinting, most antibodies derived from memory B cells or plasma cells of Omicron breakthrough cases cross-react with the Wuhan-Hu-1, BA.1, BA.2, and BA.4/5 receptor-binding domains, whereas Omicron primary infections elicit B cells of narrow specificity up to 6 months after infection. Although most clinical antibodies have reduced neutralization of Omicron, we identified an ultrapotent pan-variant-neutralizing antibody that is a strong candidate for clinical development. Imprinted antibody responses against SARS-CoV-2 Omicron sublineages.,Park YJ, Pinto D, Walls AC, Liu Z, De Marco A, Benigni F, Zatta F, Silacci-Fregni C, Bassi J, Sprouse KR, Addetia A, Bowen JE, Stewart C, Giurdanella M, Saliba C, Guarino B, Schmid MA, Franko NM, Logue JK, Dang HV, Hauser K, di Iulio J, Rivera W, Schnell G, Rajesh A, Zhou J, Farhat N, Kaiser H, Montiel-Ruiz M, Noack J, Lempp FA, Janer J, Abdelnabi R, Maes P, Ferrari P, Ceschi A, Giannini O, de Melo GD, Kergoat L, Bourhy H, Neyts J, Soriaga L, Purcell LA, Snell G, Whelan SPJ, Lanzavecchia A, Virgin HW, Piccoli L, Chu HY, Pizzuto MS, Corti D, Veesler D Science. 2022 Nov 11;378(6620):619-627. doi: 10.1126/science.adc9127. Epub 2022 , Oct 20. PMID:36264829[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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