8gs6
Structure of the SARS-CoV-2 BA.2.75 spike glycoprotein (closed state 1)Structure of the SARS-CoV-2 BA.2.75 spike glycoprotein (closed state 1)
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 SARS-CoV-2 Omicron BA.2.75 variant emerged in May 2022. BA.2.75 is a BA.2 descendant but is phylogenetically distinct from BA.5, the currently predominant BA.2 descendant. Here, we show that BA.2.75 has a greater effective reproduction number and different immunogenicity profile than BA.5. We determined the sensitivity of BA.2.75 to vaccinee and convalescent sera as well as a panel of clinically available antiviral drugs and antibodies. Antiviral drugs largely retained potency, but antibody sensitivity varied depending on several key BA.2.75-specific substitutions. The BA.2.75 spike exhibited a profoundly higher affinity for its human receptor, ACE2. Additionally, the fusogenicity, growth efficiency in human alveolar epithelial cells, and intrinsic pathogenicity in hamsters of BA.2.75 were greater than those of BA.2. Our multilevel investigations suggest that BA.2.75 acquired virological properties independent of BA.5, and the potential risk of BA.2.75 to global health is greater than that of BA.5. Virological characteristics of the SARS-CoV-2 Omicron BA.2.75 variant.,Saito A, Tamura T, Zahradnik J, Deguchi S, Tabata K, Anraku Y, Kimura I, Ito J, Yamasoba D, Nasser H, Toyoda M, Nagata K, Uriu K, Kosugi Y, Fujita S, Shofa M, Monira Begum M, Shimizu R, Oda Y, Suzuki R, Ito H, Nao N, Wang L, Tsuda M, Yoshimatsu K, Kuramochi J, Kita S, Sasaki-Tabata K, Fukuhara H, Maenaka K, Yamamoto Y, Nagamoto T, Asakura H, Nagashima M, Sadamasu K, Yoshimura K, Ueno T, Schreiber G, Takaori-Kondo A, Shirakawa K, Sawa H, Irie T, Hashiguchi T, Takayama K, Matsuno K, Tanaka S, Ikeda T, Fukuhara T, Sato K Cell Host Microbe. 2022 Nov 9;30(11):1540-1555.e15. doi: , 10.1016/j.chom.2022.10.003. Epub 2022 Oct 18. PMID:36272413[4] From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine. References
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