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Crystal structure of HCoV-HKU1 spike stem helix peptide in complex with Fab of broadly neutralizing antibody CC95.108 isolated from a vaccinated COVID-19 convalescent
Structural highlights
FunctionSPIKE_CVHN1 S1 attaches the virion to the cell membrane by interacting with cell receptors, initiating the infection. S2 is a class I viral fusion protein. Under the current model, the protein has at least 3 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. Presumably interacts with target cell lipid raft after cell attachment (By similarity). Publication Abstract from PubMedPan-betacoronavirus neutralizing antibodies may hold the key to developing broadly protective vaccines against novel pandemic coronaviruses and to more effectively respond to SARS-CoV-2 variants. The emergence of Omicron and subvariants of SARS-CoV-2 illustrates the limitations of solely targeting the receptor-binding domain (RBD) of the spike (S) protein. Here, we isolated a large panel of broadly neutralizing antibodies (bnAbs) from SARS-CoV-2 recovered-vaccinated donors, which targets a conserved S2 region in the betacoronavirus spike fusion machinery. Select bnAbs showed broad in vivo protection against all three deadly betacoronaviruses, SARS-CoV-1, SARS-CoV-2, and MERS-CoV, which have spilled over into humans in the past two decades. Structural studies of these bnAbs delineated the molecular basis for their broad reactivity and revealed common antibody features targetable by broad vaccination strategies. These bnAbs provide new insights and opportunities for antibody-based interventions and for developing pan-betacoronavirus vaccines. Broadly neutralizing anti-S2 antibodies protect against all three human betacoronaviruses that cause deadly disease.,Zhou P, Song G, Liu H, Yuan M, He WT, Beutler N, Zhu X, Tse LV, Martinez DR, Schafer A, Anzanello F, Yong P, Peng L, Dueker K, Musharrafieh R, Callaghan S, Capozzola T, Limbo O, Parren M, Garcia E, Rawlings SA, Smith DM, Nemazee D, Jardine JG, Safonova Y, Briney B, Rogers TF, Wilson IA, Baric RS, Gralinski LE, Burton DR, Andrabi R Immunity. 2023 Mar 14;56(3):669-686.e7. doi: 10.1016/j.immuni.2023.02.005. Epub , 2023 Feb 16. PMID:36889306[1] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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