SARS-CoV-2 spike S375F mutation characterizes the Omicron BA.1 variant

Kimura, Izumi; Yamasoba, Daichi; Nasser, Hesham; Zahradník, Jiří; Kosugi, Yusuke; Wu, Jiaqi; Nagata, Kayoko; Uriu, Keiya; Tanaka, Yuri; Ito, Jumpei; Shimizu, Ryo; Tan, Toong Seng; Butlertanaka, Erika P.; Asakura, Hiroyuki; Sadamasu, Kenji; Yoshimura, Kazuhisa; Ueno, Takamasa; Takaori‐Kondo, Akifumi; Schreiber, Gideon; Toyoda, Mako; Shirakawa, Kotaro; Irie, Takashi; Saito, Akatsuki; Nakagawa, So; Ikeda, Terumasa; Sato, Kei

doi:10.1101/2022.04.03.486864

Cited by 14 publications

(46 citation statements)

References 60 publications

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“…Pseudoviruses were prepared as previously described (Kimura et al, 2022a;Meng et al, 2022;Ozono et al, 2021;Saito et al, 2022;Uriu et al, 2021;Yamasoba et al, 2022a;Yamasoba et al, 2022b). Briefly, lentivirus (HIV-1)-based, luciferase-expressing reporter viruses were pseudotyped with the SARS-CoV-2 S proteins.…”

Section: Neutralization Assaymentioning

confidence: 99%

“…Neutralization assay (Figure 2) was prepared as previously described (Kimura et al, 2022a;Meng et al, 2022;Ozono et al, 2021;Saito et al, 2022;Uriu et al, 2021;Yamasoba et al, 2022a;Yamasoba et al, 2022b). Briefly, the SARS-CoV-2 S pseudoviruses (counting ~20,000 relative light units) were incubated with serially diluted (120-fold to 97,480-fold dilution at the final concentration) heat-inactivated sera at 37°C for 1 hour.…”

Section: Neutralization Assaymentioning

confidence: 99%

“…To induce eUnaG2 reporter protein fluorescence, bilirubin (Sigma-Aldrich, Cat# 14370-1G) was added to the final concentration of 5 nM. RBD expression and ACE2 signal were recorded by using a FACS S3e cell sorter device (Bio-Rad), background binding signals were subtracted and data were fitted to a standard noncooperative Hill equation by nonlinear least-squares regression using Python v3.7 (https://www.python.org) as previously described (Kimura et al, 2022a;Kimura et al, 2022b;Motozono et al, 2021;Yamasoba et al, 2022a;Zahradnik et al, 2021b). SARS-CoV-2 S-based fusion assay SARS-CoV-2 S-based fusion assay (Figures 3D and S2C) was performed as previously described (Kimura et al, 2022b;Motozono et al, 2021;Saito et al, 2022;Suzuki et al, 2022;Yamasoba et al, 2022a).…”

Section: Yeast Surface Displaymentioning

confidence: 99%

“…RBD expression and ACE2 signal were recorded by using a FACS S3e cell sorter device (Bio-Rad), background binding signals were subtracted and data were fitted to a standard noncooperative Hill equation by nonlinear least-squares regression using Python v3.7 (https://www.python.org) as previously described (Kimura et al, 2022a;Kimura et al, 2022b;Motozono et al, 2021;Yamasoba et al, 2022a;Zahradnik et al, 2021b). SARS-CoV-2 S-based fusion assay SARS-CoV-2 S-based fusion assay (Figures 3D and S2C) was performed as previously described (Kimura et al, 2022b;Motozono et al, 2021;Saito et al, 2022;Suzuki et al, 2022;Yamasoba et al, 2022a). Briefly, on day 1, effector cells (i.e., S-expressing cells) and target cells (see below) were prepared at a density of 0.6-0.8 × 10 6 cells in a 6-well plate.…”

Section: Yeast Surface Displaymentioning

confidence: 99%

“…Resistance to antiviral humoral immunity can be mainly determined by the mutations in the S protein. For instance, Omicron BA.1 exhibits profound resistance to neutralizing antibodies induced by vaccination and natural SARS-CoV-2 infection as well as therapeutic monoclonal antibodies (Cao et al, 2021;Cele et al, 2021;Dejnirattisai et al, 2022;Garcia-Beltran et al, 2021;Liu et al, 2021;Meng et al, 2022;Planas et al, 2021;Takashita et al, 2022a;VanBlargan et al, 2022) and BA.2 (Bruel et al, 2022;Takashita et al, 2022b;Yamasoba et al, 2022a;Yamasoba et al, 2022b). In addition to immune evasion, the mutations in the S protein potentially modulate viral pathogenicity.…”

Section: Introductionmentioning

confidence: 99%

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Virological characteristics of the novel SARS-CoV-2 Omicron variants including BA.2.12.1, BA.4 and BA.5

Kimura

Yamasoba

Tamura

et al. 2022

Preprint

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166

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After the global spread of SARS-CoV-2 Omicron BA.2 lineage, some BA.2-related variants that acquire mutations in the L452 residue of spike protein, such as BA.2.9.1 and BA.2.13 (L452M), BA.2.12.1 (L452Q), and BA.2.11, BA.4 and BA.5 (L452R), emerged in multiple countries. Our statistical analysis showed that the effective reproduction numbers of these L452R/M/Q-bearing BA.2-related Omicron variants are greater than that of the original BA.2. Neutralization experiments revealed that the immunity induced by BA.1 and BA.2 infections is less effective against BA.4/5. Cell culture experiments showed that BA.2.12.1 and BA.4/5 replicate more efficiently in human alveolar epithelial cells than BA.2, and particularly, BA.4/5 is more fusogenic than BA.2. Furthermore, infection experiments using hamsters indicated that BA.4/5 is more pathogenic than BA.2. Altogether, our multiscale investigations suggest that the risk of L452R/M/Q-bearing BA.2-related Omicron variants, particularly BA.4 and BA.5, to global health is potentially greater than that of original BA.2.HighlightsSpike L452R/Q/M mutations increase the effective reproduction number of BA.2BA.4/5 is resistant to the immunity induced by BA.1 and BA.2 infectionsBA.2.12.1 and BA.4/5 more efficiently spread in human lung cells than BA.2BA.4/5 is more pathogenic than BA.2 in hamsters

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Section: Neutralization Assaymentioning

confidence: 99%

Section: Neutralization Assaymentioning

confidence: 99%

Section: Yeast Surface Displaymentioning

confidence: 99%

Section: Yeast Surface Displaymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Virological characteristics of the novel SARS-CoV-2 Omicron variants including BA.2.12.1, BA.4 and BA.5

Kimura

Yamasoba

Tamura

et al. 2022

Preprint

Self Cite

166

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show abstract

A Class of Shark‐Derived Single‐Domain Antibodies can Broadly Neutralize SARS‐Related Coronaviruses and the Structural Basis of Neutralization and Omicron Escape

et al. 2022

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Many SARS-CoV-2 variants appeared under selective pressure from host immunity with high infectivity and immune evasion, such as the Alpha (B.1.1.7), [3,4] Beta (B.1.351), [5] Delta (B.1.617.2), [6] Gamma (P.1) [7] and Omicron (B.1.1.529). [8] These variants brought considerable challenges to the prevention and treatment of SARS-CoV-2 infections. Effective and affordable preventive and therapeutic strategies are urgently needed. Understanding mechanisms of virus neutralization and the escape will expedite our effort in virus prevention and therapy.In addition to the active immunity brought by vaccination, the passive immunity of neutralizing antibodies can play an important role in preventing and treating infectious diseases. The vaccine's protective effect is greatly reduced in people with weakened immune systems, such as elderly and people with immune-compromised conditions. In this case, the role of passive immunity is significant. The convalescent serum has been used to treat COVID-19 patients with a considerable effect but is limited by the scarcity of sources and possible side effects. [9,10] The identification of a novel class of shark-derived single domain antibodies, named vnarbodies that show picomolar affinities binding to the receptor binding domain (RBD) of Wuhan and Alpha, Beta, Kappa, Delta, Delta-plus, and Lambda variants, is reported. Vnarbody 20G6 and 17F6 have broad neutralizing activities against all these SARS-CoV-2 viruses as well as other sarbecoviruses, including Pangolin coronavirus and Bat coronavirus. Intranasal administration of 20G6 effectively protects mice from the challenges of SARS-CoV-2 Wuhan and Beta variants. 20G6 and 17F6 contain a unique "WXGY" motif in the complementary determining region 3 that binds to a hidden epitope on RBD, which is highly conserved in sarbecoviruses through a novel β-sheet interaction. It is found that the S375F mutation on Omicron RBD disrupts the structure of β-strand, thus impair the binding with 20G6. The study demonstrates that shark-derived vnarbodies offer a prophylactic and therapeutic option against most SARS-CoV-2 variants and provide insights into antibody evasion by the Omicron variant.The ORCID identification number(s) for the author(s) of this article can be found under https://doi.org/10.1002/smtd.202200387.

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SARS-CoV-2 spike N-terminal domain modulates TMPRSS2-dependent viral entry and fusogenicity

Meng¹,

Datir²,

Choi³

et al. 2022

Cell Reports

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SARS-CoV-2 spike S375F mutation characterizes the Omicron BA.1 variant

Cited by 14 publications

References 60 publications

Virological characteristics of the novel SARS-CoV-2 Omicron variants including BA.2.12.1, BA.4 and BA.5

Virological characteristics of the novel SARS-CoV-2 Omicron variants including BA.2.12.1, BA.4 and BA.5

A Class of Shark‐Derived Single‐Domain Antibodies can Broadly Neutralize SARS‐Related Coronaviruses and the Structural Basis of Neutralization and Omicron Escape

SARS-CoV-2 spike N-terminal domain modulates TMPRSS2-dependent viral entry and fusogenicity

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