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• W4310676779 abstract "•Omicron spike receptor-binding domain determines virological characteristics•Spike S375F mutation results in the poor spike cleavage and fusogenicity in Omicron•Acquisition of the spike S375F mutation triggered the explosive spread of Omicron•F375-H505-mediated π-π interaction in the spike determines the phenotype of Omicron Recent studies have revealed the unique virological characteristics of Omicron, particularly those of its spike protein, such as less cleavage efficacy in cells, reduced ACE2 binding affinity, and poor fusogenicity. However, it remains unclear which mutation(s) determine these three virological characteristics of Omicron spike. Here, we show that these characteristics of the Omicron spike protein are determined by its receptor-binding domain. Of interest, molecular phylogenetic analysis revealed that acquisition of the spike S375F mutation was closely associated with the explosive spread of Omicron in the human population. We further elucidated that the F375 residue forms an interprotomer pi-pi interaction with the H505 residue of another protomer in the spike trimer, conferring the attenuated cleavage efficiency and fusogenicity of Omicron spike. Our data shed light on the evolutionary events underlying the emergence of Omicron at the molecular level. Recent studies have revealed the unique virological characteristics of Omicron, particularly those of its spike protein, such as less cleavage efficacy in cells, reduced ACE2 binding affinity, and poor fusogenicity. However, it remains unclear which mutation(s) determine these three virological characteristics of Omicron spike. Here, we show that these characteristics of the Omicron spike protein are determined by its receptor-binding domain. Of interest, molecular phylogenetic analysis revealed that acquisition of the spike S375F mutation was closely associated with the explosive spread of Omicron in the human population. We further elucidated that the F375 residue forms an interprotomer pi-pi interaction with the H505 residue of another protomer in the spike trimer, conferring the attenuated cleavage efficiency and fusogenicity of Omicron spike. Our data shed light on the evolutionary events underlying the emergence of Omicron at the molecular level. Since the emergence of SARS-CoV-2 at the end of 2019, this virus has become spectacularly diverse. In April 2022, the WHO defined two variants of concern, Delta (B.1.617.2 and AY lineages) and Omicron (originally the B.1.1.529 lineage, then reclassified into BA lineages)1WHOTracking SARS-CoV-2 Variants.https://www.who.int/en/activities/tracking-SARS-CoV-2-variants/Date: 2022Google Scholar; currently, Omicron is the predominant variant spreading worldwide. Even before detection of the Omicron B.1.1.529 lineage at the end of November 2021 in South Africa,2National Institute for Communicable Diseases, S.ANew COVID-19 Variant Detected in South Africa (November 25, 2021).https://www.nicd.ac.za/new-covid-19-variant-detected-in-south-africa/Date: 2021Google Scholar SARS-CoV-2 had become highly diversified from the original lineage, the B lineage, which was isolated in Wuhan, China, on December 24, 2019 (strain Wuhan-Hu-1, GISAID ID: EPI_ISL_402123).3Wu F. Zhao S. Yu B. Chen Y.M. Wang W. Song Z.G. Hu Y. Tao Z.W. Tian J.H. Pei Y.Y. et al.A new coronavirus associated with human respiratory disease in China.Nature. 2020; 579: 265-269https://doi.org/10.1038/s41586-020-2008-3Crossref PubMed Scopus (6247) Google Scholar Regarding the evolutionary scenario leading to the emergence of Omicron, the B.1 lineage, which had acquired the D614G mutation in the spike (S) protein,4Hou Y.J. Chiba S. Halfmann P. Ehre C. Kuroda M. Dinnon 3rd, K.H. Leist S.R. Schäfer A. Nakajima N. Takahashi K. et al.SARS-CoV-2 D614G variant exhibits efficient replication ex vivo and transmission in vivo.Science. 2020; 370: 1464-1468https://doi.org/10.1126/science.abe8499Crossref PubMed Scopus (484) Google Scholar,5Korber B. Fischer W.M. Gnanakaran S. Yoon H. Theiler J. Abfalterer W. Hengartner N. Giorgi E.E. Bhattacharya T. Foley B. et al.Tracking changes in SARS-CoV-2 spike: evidence that D614G increases infectivity of the COVID-19 virus.Cell. 2020; 182: 812-827.e19https://doi.org/10.1016/j.cell.2020.06.043Abstract Full Text Full Text PDF PubMed Scopus (2238) Google Scholar,6Li Q. Wu J. Nie J. Zhang L. Hao H. Liu S. Zhao C. Zhang Q. Liu H. Nie L. et al.The impact of mutations in SARS-CoV-2 spike on viral infectivity and antigenicity.Cell. 2020; 182: 1284-1294.e9https://doi.org/10.1016/j.cell.2020.07.012Abstract Full Text Full Text PDF PubMed Scopus (877) Google Scholar,7Plante J.A. Liu Y. Liu J. Xia H. Johnson B.A. Lokugamage K.G. Zhang X. Muruato A.E. Zou J. Fontes-Garfias C.R. et al.Spike mutation D614G alters SARS-CoV-2 fitness.Nature. 2021; 592: 116-121https://doi.org/10.1038/s41586-020-2895-3Crossref PubMed Scopus (808) Google Scholar,8Yurkovetskiy L. Wang X. Pascal K.E. Tomkins-Tinch C. Nyalile T.P. Wang Y. Baum A. Diehl W.E. Dauphin A. Carbone C. et al.Structural and functional analysis of the D614G SARS-CoV-2 spike protein variant.Cell. 2020; 183: 739-751.e8https://doi.org/10.1016/j.cell.2020.09.032Abstract Full Text Full Text PDF PubMed Scopus (547) Google Scholar was first reported on January 24, 2020 (GISAID ID: EPI_ISL_451345). Thereafter, the B.1.1 lineage was first reported in England on February 16, 2020 (GISAID ID: EPI_ISL_466615). The B.1.1 lineage is the common ancestor of both Alpha (B.1.1.7 lineage), a prior variant of concern by March 2022, and Omicron (B.1.1.529 lineage), and the Alpha variant caused a large surge of infection worldwide beginning in the fall of 2020.9Davies N.G. Abbott S. Barnard R.C. et al.Estimated transmissibility and impact of SARS-CoV-2 lineage B.1.1.7 in England.Science. 2021; 372: eabg3055https://doi.org/10.1126/science.abg3055Crossref PubMed Scopus (0) Google Scholar Omicron was first reported in South Africa on September 30, 2021 (GISAID ID: EPI_ISL_7971523).2National Institute for Communicable Diseases, S.ANew COVID-19 Variant Detected in South Africa (November 25, 2021).https://www.nicd.ac.za/new-covid-19-variant-detected-in-south-africa/Date: 2021Google Scholar Soon after the press briefing on Omicron emergence on November 25, 2021,2National Institute for Communicable Diseases, S.ANew COVID-19 Variant Detected in South Africa (November 25, 2021).https://www.nicd.ac.za/new-covid-19-variant-detected-in-south-africa/Date: 2021Google Scholar the virological characteristics of Omicron, currently designated BA.1 (i.e., B.1.1.529.1 lineage, hereafter referred to as Omicron in this study), were intensively investigated. For example, Omicron exhibits profound resistance to the humoral immunity induced by vaccination and natural SARS-CoV-2 infection.10Cameroni E. Bowen J.E. Rosen L.E. Saliba C. Zepeda S.K. Culap K. Pinto D. VanBlargan L.A. De Marco A. di Iulio J. et al.Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift.Nature. 2022; 602: 664-670https://doi.org/10.1038/s41586-021-04386-2Crossref PubMed Scopus (421) Google Scholar,11Cao Y. Wang J. Jian F. Xiao T. Song W. Yisimayi A. Huang W. Li Q. Wang P. An R. et al.Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies.Nature. 2022; 602: 657-663https://doi.org/10.1038/d41586-41021-03796-41586Crossref PubMed Scopus (0) Google Scholar,12Carreño J.M. Alshammary H. Tcheou J. Singh G. Raskin A.J. Kawabata H. Sominsky L.A. Clark J.J. Adelsberg D.C. Bielak D.A. Gonzalez-Reiche A.S. et al.Activity of convalescent and vaccine serum against SARS-CoV-2 Omicron.Nature. 2022; 602: 682-688https://doi.org/10.1038/d41586-41021-03846-zCrossref PubMed Scopus (0) Google Scholar,13Cele S. Jackson L. Khoury D.S. Khan K. Moyo-Gwete T. Tegally H. San J.E. Cromer D. Scheepers C. Amoako D.G. et al.Omicron extensively but incompletely escapes Pfizer BNT162b2 neutralization.Nature. 2022; 602: 654-656https://doi.org/10.1038/d41586-41021-03824-41585Crossref PubMed Scopus (0) Google Scholar,14Dejnirattisai W. Huo J. Zhou D. Zahradník J. Supasa P. Liu C. Duyvesteyn H.M.E. Ginn H.M. Mentzer A.J. Tuekprakhon A. et al.SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses.Cell. 2022; 185: 467-484.e15https://doi.org/10.1016/j.cell.2021.12.046Abstract Full Text Full Text PDF PubMed Scopus (347) Google Scholar,15Dejnirattisai W. Shaw R.H. Supasa P. Liu C. Stuart A.S. Pollard A.J. Liu X. Lambe T. Crook D. Stuart D.I. et al.Reduced neutralisation of SARS-CoV-2 omicron B.1.1.529 variant by post-immunisation serum.Lancet. 2022; 399: 234-236https://doi.org/10.1016/S0140-6736(1021)02844-02840Crossref PubMed Scopus (0) Google Scholar,16Garcia-Beltran W.F. Denis K.J.S. Hoelzemer A. Lam E.C. Nitido A.D. Sheehan M.L. Berrios C. Ofoman O. Chang C.C. Hauser B.M. et al.mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant.medRxiv. 2021; (Preprint at)https://doi.org/10.1016/j.cell.2021.1012.1033Crossref Google Scholar,17Liu L. Iketani S. Guo Y. Chan J.F.W. Wang M. Liu L. Luo Y. Chu H. Huang Y. Nair M.S. et al.Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2.Nature. 2022; 602: 676-681https://doi.org/10.1038/d41586-41021-03826-41583Crossref PubMed Scopus (0) Google Scholar,18Meng B. Abdullahi A. Ferreira I.A.T.M. Goonawardane N. Saito A. Kimura I. Yamasoba D. Gerber P.P. Fatihi S. Rathore S. et al.Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts tropism and fusogenicity.Nature. 2022; 603: 706-714https://doi.org/10.1038/s41586-022-04474-xCrossref PubMed Scopus (240) Google Scholar,19Planas D. Saunders N. Maes P. Guivel-Benhassine F. Planchais C. Buchrieser J. Bolland W.H. Porrot F. Staropoli I. Lemoine F. et al.Considerable escape of SARS-CoV-2 Omicron to antibody neutralization.Nature. 2022; 602: 671-675https://doi.org/10.1038/d41586-41021-03827-41582Crossref PubMed Scopus (0) Google Scholar,20Takashita E. Kinoshita N. Yamayoshi S. Sakai-Tagawa Y. Fujisaki S. Ito M. Iwatsuki-Horimoto K. Chiba S. Halfmann P. Nagai H. et al.Efficacy of antibodies and antiviral drugs against Covid-19 Omicron variant.N. Engl. J. Med. 2022; 386: 995-998https://doi.org/10.1056/NEJMc2119407Crossref PubMed Scopus (143) Google Scholar,21VanBlargan L.A. Errico J.M. Halfmann P.J. Zost S.J. Crowe Jr., J.E. Purcell L.A. Kawaoka Y. Corti D. Fremont D.H. Diamond M.S. An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by therapeutic monoclonal antibodies.Nat. Med. 2022; 28: 490-495https://doi.org/10.1038/s41591-021-01678-yCrossref PubMed Scopus (265) Google Scholar In addition, we demonstrated that the Omicron spike (S) protein is less prone to cleavage by furin, a cellular protease, and exhibits poor fusogenicity.18Meng B. Abdullahi A. Ferreira I.A.T.M. Goonawardane N. Saito A. Kimura I. Yamasoba D. Gerber P.P. Fatihi S. Rathore S. et al.Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts tropism and fusogenicity.Nature. 2022; 603: 706-714https://doi.org/10.1038/s41586-022-04474-xCrossref PubMed Scopus (240) Google Scholar,22Suzuki R. Yamasoba D. Kimura I. Wang L. Kishimoto M. Ito J. Morioka Y. Nao N. Nasser H. Uriu K. et al.Attenuated fusogenicity and pathogenicity of SARS-CoV-2 Omicron variant.Nature. 2022; 603: 700-705https://doi.org/10.1038/s41586-022-04462-1Crossref PubMed Scopus (128) Google Scholar Moreover, we showed that the binding affinity of the receptor-binding domain (RBD) of Omicron S to human ACE2 is significantly lower than that of ancestral B.1 S.14Dejnirattisai W. Huo J. Zhou D. Zahradník J. Supasa P. Liu C. Duyvesteyn H.M.E. Ginn H.M. Mentzer A.J. Tuekprakhon A. et al.SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses.Cell. 2022; 185: 467-484.e15https://doi.org/10.1016/j.cell.2021.12.046Abstract Full Text Full Text PDF PubMed Scopus (347) Google Scholar,23Yamasoba D. Kimura I. Nasser H. Morioka Y. Nao N. Ito J. Uriu K. Tsuda M. Zahradnik J. Shirakawa K. et al.Virological characteristics of the SARS-CoV-2 Omicron BA.2 spike.Cell. 2022; 185: 2103-2115.e19https://doi.org/10.1016/j.cell.2022.04.035Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar However, it remains unclear why Omicron has spread so rapidly worldwide. In particular, although the explosive infectious spread of Omicron in the human population can be mainly characterized by the virological properties of Omicron S, the mutation(s) in Omicron S that are responsible for its virological characteristics, such as inefficient S cleavage, lower fusogenicity, reduced ACE2 binding affinity and profound immune resistance, have not been well elucidated. In this study, we first demonstrate that the representative characteristics of Omicron S, such as immune resistance, poor S cleavage efficiency and poor fusogenicity, are determined by its RBD. Based on molecular phylogenetic analysis, we show that acquisition of the S375F mutation in the Omicron RBD is closely associated with its explosive spread. Moreover, we experimentally demonstrate that the S375F mutation is critical for the virological properties of Omicron S, namely, attenuation of S cleavage efficiency and fusogenicity as well as the decrease in ACE2 binding affinity. Furthermore, we determined how attenuated S cleavage and fusogenicity are conferred by the S375F mutation. To determine the mutation(s) responsible for the virological features of Omicron, we prepared a series of expression plasmids for Omicron S-based chimeric mutants with swapping of the N-terminal domain (NTD) and/or RBD of B.1 (D614G-bearing strain) S (Figure 1A ). Experiments showed that pseudoviruses with B.1 RBD-bearing Omicron S [Omicron S/B.1 S_RBD (spike 4 in Figure 1A) and Omicron S/B.1 S_NTD+RBD (spike 5)] exhibited increased infectivity compared to pseudovirus with Omicron S (spike 2) in HOS-ACE2/TMPRSS2 cells (Figure 1B) and A549-ACE2 cells (Figure S1A). Western blot analysis (Figure 1C) showed that the S cleavage efficacy in cells (Figure 1D, left) correlated with the level in virion-incorporated S2 protein (Figure 1D, right) and pseudovirus infectivity (Figure 1B). In particular, the cleavage efficacy of Omicron S was lower than that of B.1 S, which is consistent with our recent studies (spikes 1 and 2 in Figures 1C and 1D).18Meng B. Abdullahi A. Ferreira I.A.T.M. Goonawardane N. Saito A. Kimura I. Yamasoba D. Gerber P.P. Fatihi S. Rathore S. et al.Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts tropism and fusogenicity.Nature. 2022; 603: 706-714https://doi.org/10.1038/s41586-022-04474-xCrossref PubMed Scopus (240) Google Scholar,22Suzuki R. Yamasoba D. Kimura I. Wang L. Kishimoto M. Ito J. Morioka Y. Nao N. Nasser H. Uriu K. et al.Attenuated fusogenicity and pathogenicity of SARS-CoV-2 Omicron variant.Nature. 2022; 603: 700-705https://doi.org/10.1038/s41586-022-04462-1Crossref PubMed Scopus (128) Google Scholar,23Yamasoba D. Kimura I. Nasser H. Morioka Y. Nao N. Ito J. Uriu K. Tsuda M. Zahradnik J. Shirakawa K. et al.Virological characteristics of the SARS-CoV-2 Omicron BA.2 spike.Cell. 2022; 185: 2103-2115.e19https://doi.org/10.1016/j.cell.2022.04.035Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar On the other hand, chimeric Omicron S proteins bearing the B.1 RBD (spikes 4 and 5) displayed increased cleavage efficacy (Figures 1C and 1D). Although the surface expression levels of a series of Omicron S chimeras bearing the B.1 domains (spikes 3–5) were lower than those of Omicron S chimeras (Figure 1E), a cell-based fusion assay18Meng B. Abdullahi A. Ferreira I.A.T.M. Goonawardane N. Saito A. Kimura I. Yamasoba D. Gerber P.P. Fatihi S. Rathore S. et al.Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts tropism and fusogenicity.Nature. 2022; 603: 706-714https://doi.org/10.1038/s41586-022-04474-xCrossref PubMed Scopus (240) Google Scholar,22Suzuki R. Yamasoba D. Kimura I. Wang L. Kishimoto M. Ito J. Morioka Y. Nao N. Nasser H. Uriu K. et al.Attenuated fusogenicity and pathogenicity of SARS-CoV-2 Omicron variant.Nature. 2022; 603: 700-705https://doi.org/10.1038/s41586-022-04462-1Crossref PubMed Scopus (128) Google Scholar,23Yamasoba D. Kimura I. Nasser H. Morioka Y. Nao N. Ito J. Uriu K. Tsuda M. Zahradnik J. Shirakawa K. et al.Virological characteristics of the SARS-CoV-2 Omicron BA.2 spike.Cell. 2022; 185: 2103-2115.e19https://doi.org/10.1016/j.cell.2022.04.035Abstract Full Text Full Text PDF PubMed Scopus (74) Google Scholar,24Motozono C. Toyoda M. Zahradnik J. Saito A. Nasser H. Tan T.S. Ngare I. Kimura I. Uriu K. Kosugi Y. et al.SARS-CoV-2 spike L452R variant evades cellular immunity and increases infectivity.Cell Host Microbe. 2021; 29: 1124-1136.e11https://doi.org/10.1016/j.chom.2021.06.006Abstract Full Text Full Text PDF PubMed Scopus (205) Google Scholar revealed that the fusogenicity of B.1 RBD-bearing Omicron S was significantly higher than parental Omicron S (Figure 1F). To verify the importance of the RBD for the phenotype of Omicron S, we performed reversal experiments based on B.1 S [B.1 S/Omicron S_RBD (spike 6) in Figure 1A]. Corresponding to the results for Omicron S, the pseudovirus infectivity (Figure 1B), S cleavage efficacy (Figures 1C and 1D), and fusogenicity (Figure 1F) of Omicron RBD-harboring S [B.1 S/Omicron S_RBD (spike 6)] were attenuated compared to those of parental B.1 S. These results suggest that the RBD of Omicron S mainly determines the attenuated cleavage efficacy and decreased fusogenicity of Omicron S. To further investigate the impact of the Omicron S RBD on multicycle viral replication, we generated a series of recombinant chimeric SARS-CoV-2 strains by reverse genetics (Figure 1G).25Torii S. Ono C. Suzuki R. Morioka Y. Anzai I. Fauzyah Y. Maeda Y. Kamitani W. Fukuhara T. Matsuura Y. Establishment of a reverse genetics system for SARS-CoV-2 using circular polymerase extension reaction.Cell Rep. 2021; 35: 109014Abstract Full Text Full Text PDF PubMed Scopus (30) Google Scholar As shown in Figure 1H, the growth of rOmicron S-GFP (virus II) and rOmicron S/B.1 S_NTD (virus III) was lower than that of rB.1 S-GFP (virus I). In sharp contrast, recombinant viruses bearing the B.1 RBD [rOmicron S/B.1_RBD-GFP (virus IV) and rOmicron S/B.1 S_NTD+RBD-GFP (virus V)] replicated more efficiently than rOmicron S-GFP (virus II) in VeroE6/TMPRSS2 cells (Figure 1H). In addition, to monitor the spread of these recombinant viruses, we measured GFP intensity in infected cell cultures. We found that the GFP intensity of cells infected with recombinant viruses bearing the B.1 RBD was significantly higher than that of cells infected with rOmicron S-GFP (virus II) (Figures 1I and S1B). These data suggest that the RBD of Omicron S attenuates viral growth capacity in cell cultures. We then measured the number of GFP-positive cells to evaluate the fusogenicity of the chimeric viruses. As shown in Figure 1J, the GFP-positive area of cells infected with the recombinant viruses at 48 h post infection (h.p.i.) was significantly larger for viruses bearing the B.1 RBD [rOmicron S/B.1_RBD-GFP (virus IV) and rOmicron S/B.1 S_NTD+RBD-GFP (virus V)] than for rOmicron-GFP (virus II). Consistent with the results in cells transfected with S expression plasmids (Figure 1F), these findings suggest that the Omicron RBD attenuates viral fusogenicity. Moreover, the plaques formed by infection with rOmicron S/B.1 S_RBD-GFP (virus IV) and rOmicron S/B.1 S_NTD+RBD-GFP (virus V) were significantly larger than those formed by rOmicron S-GFP virus (virus II), though the plaques formed by rOmicron S-GFP (virus II) and rOmicron S/B.1 S_NTD-GFP (virus III) were comparable (Figure 1K). Altogether, these results suggest that the Omicron RBD determines the virological features of this viral lineage, such as the observed attenuation of S1/S2 cleavage efficacy and fusogenicity. We next assessed the domains of Omicron S that are associated with the profound immune resistance of Omicron.10Cameroni E. Bowen J.E. Rosen L.E. Saliba C. Zepeda S.K. Culap K. Pinto D. VanBlargan L.A. De Marco A. di Iulio J. et al.Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift.Nature. 2022; 602: 664-670https://doi.org/10.1038/s41586-021-04386-2Crossref PubMed Scopus (421) Google Scholar,11Cao Y. Wang J. Jian F. Xiao T. Song W. Yisimayi A. Huang W. Li Q. Wang P. An R. et al.Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies.Nature. 2022; 602: 657-663https://doi.org/10.1038/d41586-41021-03796-41586Crossref PubMed Scopus (0) Google Scholar,12Carreño J.M. Alshammary H. Tcheou J. Singh G. Raskin A.J. Kawabata H. Sominsky L.A. Clark J.J. Adelsberg D.C. Bielak D.A. Gonzalez-Reiche A.S. et al.Activity of convalescent and vaccine serum against SARS-CoV-2 Omicron.Nature. 2022; 602: 682-688https://doi.org/10.1038/d41586-41021-03846-zCrossref PubMed Scopus (0) Google Scholar,13Cele S. Jackson L. Khoury D.S. Khan K. Moyo-Gwete T. Tegally H. San J.E. Cromer D. Scheepers C. Amoako D.G. et al.Omicron extensively but incompletely escapes Pfizer BNT162b2 neutralization.Nature. 2022; 602: 654-656https://doi.org/10.1038/d41586-41021-03824-41585Crossref PubMed Scopus (0) Google Scholar,14Dejnirattisai W. Huo J. Zhou D. Zahradník J. Supasa P. Liu C. Duyvesteyn H.M.E. Ginn H.M. Mentzer A.J. Tuekprakhon A. et al.SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses.Cell. 2022; 185: 467-484.e15https://doi.org/10.1016/j.cell.2021.12.046Abstract Full Text Full Text PDF PubMed Scopus (347) Google Scholar,15Dejnirattisai W. Shaw R.H. Supasa P. Liu C. Stuart A.S. Pollard A.J. Liu X. Lambe T. Crook D. Stuart D.I. et al.Reduced neutralisation of SARS-CoV-2 omicron B.1.1.529 variant by post-immunisation serum.Lancet. 2022; 399: 234-236https://doi.org/10.1016/S0140-6736(1021)02844-02840Crossref PubMed Scopus (0) Google Scholar,16Garcia-Beltran W.F. Denis K.J.S. Hoelzemer A. Lam E.C. Nitido A.D. Sheehan M.L. Berrios C. Ofoman O. Chang C.C. Hauser B.M. et al.mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant.medRxiv. 2021; (Preprint at)https://doi.org/10.1016/j.cell.2021.1012.1033Crossref Google Scholar,17Liu L. Iketani S. Guo Y. Chan J.F.W. Wang M. Liu L. Luo Y. Chu H. Huang Y. Nair M.S. et al.Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2.Nature. 2022; 602: 676-681https://doi.org/10.1038/d41586-41021-03826-41583Crossref PubMed Scopus (0) Google Scholar,18Meng B. Abdullahi A. Ferreira I.A.T.M. Goonawardane N. Saito A. Kimura I. Yamasoba D. Gerber P.P. Fatihi S. Rathore S. et al.Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts tropism and fusogenicity.Nature. 2022; 603: 706-714https://doi.org/10.1038/s41586-022-04474-xCrossref PubMed Scopus (240) Google Scholar,19Planas D. Saunders N. Maes P. Guivel-Benhassine F. Planchais C. Buchrieser J. Bolland W.H. Porrot F. Staropoli I. Lemoine F. et al.Considerable escape of SARS-CoV-2 Omicron to antibody neutralization.Nature. 2022; 602: 671-675https://doi.org/10.1038/d41586-41021-03827-41582Crossref PubMed Scopus (0) Google Scholar,20Takashita E. Kinoshita N. Yamayoshi S. Sakai-Tagawa Y. Fujisaki S. Ito M. Iwatsuki-Horimoto K. Chiba S. Halfmann P. Nagai H. et al.Efficacy of antibodies and antiviral drugs against Covid-19 Omicron variant.N. Engl. J. Med. 2022; 386: 995-998https://doi.org/10.1056/NEJMc2119407Crossref PubMed Scopus (143) Google Scholar,21VanBlargan L.A. Errico J.M. Halfmann P.J. Zost S.J. Crowe Jr., J.E. Purcell L.A. Kawaoka Y. Corti D. Fremont D.H. Diamond M.S. An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by therapeutic monoclonal antibodies.Nat. Med. 2022; 28: 490-495https://doi.org/10.1038/s41591-021-01678-yCrossref PubMed Scopus (265) Google Scholar Because swapping of Omicron S with the B.1 S NTD (Omicron S/B.1 S_NTD, spike 3) severely decreased pseudovirus infectivity (Figure 1B), we performed neutralization assays using pseudoviruses with Omicron RBD-bearing B.1 S [Omicron S/B.1 S_RBD (spike 4)] and Omicron S/B.1 S_NTD+RBD (spike 5) as well as the S proteins of Omicron (spike 2), Delta and B.1 (spike 1) (the list of sera used is shown in Table S1). Consistent with recent studies,10Cameroni E. Bowen J.E. Rosen L.E. Saliba C. Zepeda S.K. Culap K. Pinto D. VanBlargan L.A. De Marco A. di Iulio J. et al.Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift.Nature. 2022; 602: 664-670https://doi.org/10.1038/s41586-021-04386-2Crossref PubMed Scopus (421) Google Scholar,11Cao Y. Wang J. Jian F. Xiao T. Song W. Yisimayi A. Huang W. Li Q. Wang P. An R. et al.Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies.Nature. 2022; 602: 657-663https://doi.org/10.1038/d41586-41021-03796-41586Crossref PubMed Scopus (0) Google Scholar,12Carreño J.M. Alshammary H. Tcheou J. Singh G. Raskin A.J. Kawabata H. Sominsky L.A. Clark J.J. Adelsberg D.C. Bielak D.A. Gonzalez-Reiche A.S. et al.Activity of convalescent and vaccine serum against SARS-CoV-2 Omicron.Nature. 2022; 602: 682-688https://doi.org/10.1038/d41586-41021-03846-zCrossref PubMed Scopus (0) Google Scholar,13Cele S. Jackson L. Khoury D.S. Khan K. Moyo-Gwete T. Tegally H. San J.E. Cromer D. Scheepers C. Amoako D.G. et al.Omicron extensively but incompletely escapes Pfizer BNT162b2 neutralization.Nature. 2022; 602: 654-656https://doi.org/10.1038/d41586-41021-03824-41585Crossref PubMed Scopus (0) Google Scholar,14Dejnirattisai W. Huo J. Zhou D. Zahradník J. Supasa P. Liu C. Duyvesteyn H.M.E. Ginn H.M. Mentzer A.J. Tuekprakhon A. et al.SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses.Cell. 2022; 185: 467-484.e15https://doi.org/10.1016/j.cell.2021.12.046Abstract Full Text Full Text PDF PubMed Scopus (347) Google Scholar,15Dejnirattisai W. Shaw R.H. Supasa P. Liu C. Stuart A.S. Pollard A.J. Liu X. Lambe T. Crook D. Stuart D.I. et al.Reduced neutralisation of SARS-CoV-2 omicron B.1.1.529 variant by post-immunisation serum.Lancet. 2022; 399: 234-236https://doi.org/10.1016/S0140-6736(1021)02844-02840Crossref PubMed Scopus (0) Google Scholar,16Garcia-Beltran W.F. Denis K.J.S. Hoelzemer A. Lam E.C. Nitido A.D. Sheehan M.L. Berrios C. Ofoman O. Chang C.C. Hauser B.M. et al.mRNA-based COVID-19 vaccine boosters induce neutralizing immunity against SARS-CoV-2 Omicron variant.medRxiv. 2021; (Preprint at)https://doi.org/10.1016/j.cell.2021.1012.1033Crossref Google Scholar,17Liu L. Iketani S. Guo Y. Chan J.F.W. Wang M. Liu L. Luo Y. Chu H. Huang Y. Nair M.S. et al.Striking antibody evasion manifested by the Omicron variant of SARS-CoV-2.Nature. 2022; 602: 676-681https://doi.org/10.1038/d41586-41021-03826-41583Crossref PubMed Scopus (0) Google Scholar,18Meng B. Abdullahi A. Ferreira I.A.T.M. Goonawardane N. Saito A. Kimura I. Yamasoba D. Gerber P.P. Fatihi S. Rathore S. et al.Altered TMPRSS2 usage by SARS-CoV-2 Omicron impacts tropism and fusogenicity.Nature. 2022; 603: 706-714https://doi.org/10.1038/s41586-022-04474-xCrossref PubMed Scopus (240) Google Scholar,19Planas D. Saunders N. Maes P. Guivel-Benhassine F. Planchais C. Buchrieser J. Bolland W.H. Porrot F. Staropoli I. Lemoine F. et al.Considerable escape of SARS-CoV-2 Omicron to antibody neutralization.Nature. 2022; 602: 671-675https://doi.org/10.1038/d41586-41021-03827-41582Crossref PubMed Scopus (0) Google Scholar,20Takashita E. Kinoshita N. Yamayoshi S. Sakai-Tagawa Y. Fujisaki S. Ito M. Iwatsuki-Horimoto K. Chiba S. Halfmann P. Nagai H. et al.Efficacy of antibodies and antiviral drugs against Covid-19 Omicron variant.N. Engl. J. Med. 2022; 386: 995-998https://doi.org/10.1056/NEJMc2119407Crossref PubMed Scopus (143) Google Scholar,21VanBlargan L.A. Errico J.M. Halfmann P.J. Zost S.J. Crowe Jr., J.E. Purcell L.A. Kawaoka Y. Corti D. Fremont D.H. Diamond M.S. An infectious SARS-CoV-2 B.1.1.529 Omicron virus escapes neutralization by therapeutic monoclonal antibodies.Nat. Med. 2022; 28: 490-495https://doi.org/10.1038/s41591-021-01678-yCrossref PubMed Scopus (265) Google Scholar Omicron S (spike 2) was highly resistant to the vaccine sera [BNT162b2 (Figure 2A ) and mRNA-1273 (Figure 2B)] as well as convalescent sera from individuals infected with early-pandemic virus (collected before May 2020) (Figure 2C) or the Delta variant (Figure 2D). Pseudoviruses with the Omicron S/B.1 S_RBD (spike 4) and Omicron S/B.1 S_NTD+RBD (spike 5) were significantly more sensitive to vaccine sera (Figures 2A and 2B) and convalescent sera obtained from early-pandemic virus-infected patients than was Omicron S (spike 2) (Figure 2C). These results suggest that the RBD of Omicron S is closely associated with its pronounced resistance to the antiviral humoral immunity elicited by vaccination or previous SARS-CoV-2 infection. Moreover, we used convalescent sera from hamsters infected with B.1.1 (note that the S gene sequences of B.1 and B.1.1 are identical) and Omicron, as collected in our previous study,22Suzuki R. Yamasoba D. Kimura I. Wang L. Kishimoto M. Ito J. Morioka Y. Nao N. Nasser H. Uriu K. et al.Attenuated fusogenicity and pathogenicity of SARS-CoV-2 Omicron variant.Nature. 2022; 603: 700-705https://doi.org/10.1038/s41586-022-04462-1Crossref PubMed Scopus (128) Google Scholar for the assay. As shown in Figure 2E, Omicron S (spike 2) was completely resistant to the B.1.1 convalescent sera, whereas it was sensitive to the Omicron convalescent sera. Notably, chimeric Omicron S bearing the B.1 RBD [Omicron S/B.1 S_RBD (spike 4) and Omicron S/B.1 S_NTD+RBD (spike 5)] exhibited the opposite results: these chimeric pseudoviruses were sensitive to the B.1.1 convalescent sera (Figure 2E) but completely resistant to the Omicron convalescent sera (Figure 2F). These results further suggest that the Omicron RBD determines its immune resistance and is an immunodominant epitope for inducing humoral immunity. However, we found that Omicron S/B.1 S_NT" @default.
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• W4310676779 cites W1981662601 @default.
• W4310676779 cites W1990566970 @default.
• W4310676779 cites W2048162805 @default.
• W4310676779 cites W2103441770 @default.
• W4310676779 cites W2106578986 @default.
• W4310676779 cites W2108234281 @default.
• W4310676779 cites W2147660889 @default.
• W4310676779 cites W2160378127 @default.
• W4310676779 cites W2171126517 @default.
• W4310676779 cites W2256756668 @default.
• W4310676779 cites W23476114 @default.
• W4310676779 cites W2801159594 @default.
• W4310676779 cites W2807308836 @default.
• W4310676779 cites W2951912016 @default.
• W4310676779 cites W3003217347 @default.
• W4310676779 cites W3010955108 @default.
• W4310676779 cites W3039901154 @default.
• W4310676779 cites W3043431476 @default.
• W4310676779 cites W3045278468 @default.
• W4310676779 cites W3084653951 @default.
• W4310676779 cites W3093768302 @default.
• W4310676779 cites W3101992496 @default.
• W4310676779 cites W3128276018 @default.
• W4310676779 cites W3134208712 @default.
• W4310676779 cites W3137409463 @default.
• W4310676779 cites W3142564745 @default.
• W4310676779 cites W3170097501 @default.
• W4310676779 cites W3180925673 @default.
• W4310676779 cites W3193682077 @default.
• W4310676779 cites W3216478751 @default.
• W4310676779 cites W4200047841 @default.
• W4310676779 cites W4200212523 @default.
• W4310676779 cites W4205331651 @default.
• W4310676779 cites W4206079892 @default.
• W4310676779 cites W4206153788 @default.
• W4310676779 cites W4210665241 @default.
• W4310676779 cites W4210929944 @default.
• W4310676779 cites W4213305892 @default.
• W4310676779 cites W4220673385 @default.
• W4310676779 cites W4220807057 @default.
• W4310676779 cites W4220840634 @default.
• W4310676779 cites W4220904663 @default.
• W4310676779 cites W4220908383 @default.
• W4310676779 cites W4221027706 @default.
• W4310676779 cites W4221072241 @default.
• W4310676779 cites W4221116249 @default.
• W4310676779 cites W4225266546 @default.
• W4310676779 cites W4225982774 @default.
• W4310676779 cites W4226087845 @default.
• W4310676779 cites W4226087910 @default.
• W4310676779 cites W4226164088 @default.
• W4310676779 cites W4297216100 @default.
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