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Structure of SARS-CoV-2 spike in complex with antibody Fab COVIC-154
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 PubMedThe Coronavirus Immunotherapeutic Consortium (CoVIC) conducted side-by-side comparisons of over 400 anti-SARS-CoV-2 spike therapeutic antibody candidates contributed by large and small companies as well as academic groups on multiple continents. Nine reference labs analyzed antibody features, including in vivo protection in a mouse model of infection, spike protein affinity, high-resolution epitope binning, ACE-2 binding blockage, structures, and neutralization of pseudovirus and authentic virus infection, to build a publicly accessible dataset in the database CoVIC-DB. High-throughput, high-resolution binning of CoVIC antibodies defines a broad and predictive landscape of antibody epitopes on the SARS-CoV-2 spike protein and identifies features associated with durable potency against multiple SARS-CoV-2 variants of concern and high in vivo efficacy. Results of the CoVIC studies provide a guide for selecting effective and durable antibody therapeutics and for immunogen design as well as providing a framework for rapid response to future viral disease outbreaks. A global collaboration for systematic analysis of broad-ranging antibodies against the SARS-CoV-2 spike protein.,Schendel SL, Yu X, Halfmann PJ, Mahita J, Ha B, Hastie KM, Li H, Bedinger D, Troup C, Li K, Kuzmina N, Torrelles JB, Munt JE, Maddocks M, Osei-Twum M, Callaway HM, Reece S, Palser A, Kellam P, Dennison SM, Huntwork RHC, Horn GQ, Abraha M, Feeney E, Martinez-Sobrido L, Pino PA, Hicks A, Ye C, Park JG, Maingot B, Periasamy S, Mallory M, Scobey T, Lepage MN, St-Amant N, Khan S, Gambiez A, Baric RS, Bukreyev A, Gagnon L, Germann T, Kawaoka Y, Tomaras GD, Peters B, Saphire EO Cell Rep. 2025 Apr 2;44(4):115499. doi: 10.1016/j.celrep.2025.115499. PMID:40184253[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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