Virological characteristics of the SARS-CoV-2 Omicron BA.2.75 variant

Saito, Akatsuki; Tamura, Tomokazu; Zahradník, Jiří; Deguchi, Sayaka; Tabata, Koshiro; Anraku, Yuki; Kimura, Izumi; Ito, Jumpei; Yamasoba, Daichi; Nasser, Hesham; Toyoda, Mako; Nagata, Kayoko; Uriu, Keiya; Kosugi, Yusuke; Fujita, Shigeru; Shofa, Maya; Begum, MST Monira; Shimizu, Ryo; Oda, Yoshitaka; Suzuki, Rigel; Ito, Hayato; Nao, Naganori; Wang, Lei; Tsuda, Masumi; Yoshimatsu, Kumiko; Kuramochi, Jin; Kita, Shunsuke; Sasaki-Tabata, Kaori; Fukuhara, Hideo; Maenaka, Katsumi; Yamamoto, Yuki; Nagamoto, Tetsuharu; Asakura, Hiroyuki; Nagashima, Mami; Sadamasu, Kenji; Yoshimura, Kazuhisa; Ueno, Takamasa; Schreiber, Gideon; Takaori‐Kondo, Akifumi; Shirakawa, Kotaro; Sawa, Hirofumi; Irie, Takashi; Hanabusa, Takao; Takayama, Kazuo; Matsuno, Keita; Tanaka, Shinya; Ikeda, Terumasa; Fukuhara, Takasuke; Sato, Kei

doi:10.1016/j.chom.2022.10.003

Cited by 152 publications

(415 citation statements)

References 86 publications

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“…BA.4 and BA.5 replicate more efficiently than BA.2 in alveolar epithelial cells and are more fusogenic 48 . BA.2.75.2 growth efficiency in alveolar epithelial cells and spike-mediated fusion in Calu-3 cells are also higher than those of BA.2 49,50 . We did not observe an enhanced cell-cell fusogenicity of BA.2.75.2, BA.4.6.…”

Section: Discussionmentioning

confidence: 78%

Resistance of Omicron subvariants BA.2.75.2, BA.4.6 and BQ.1.1 to neutralizing antibodies

Planas

Bruel

Staropoli

et al. 2022

Preprint

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Convergent evolution of SARS-CoV-2 Omicron BA.2, BA.4 and BA.5 lineages has led to the emergence of several new subvariants, including BA.2.75.2, BA.4.6. and BQ.1.1. The subvariants BA.2.75.2 and BQ.1.1 are expected to become predominant in many countries in November 2022. They carry an additional and often redundant set of mutations in the spike, likely responsible for increased transmissibility and immune evasion. Here, we established a viral amplification procedure to easily isolate Omicron strains. We examined their sensitivity to 6 therapeutic monoclonal antibodies (mAbs) and to 72 sera from Pfizer BNT162b2-vaccinated individuals, with or without BA.1/BA.2 or BA.5 breakthrough infection. Ronapreve (Casirivimab and Imdevimab) and Evusheld (Cilgavimab and Tixagevimab) lost any antiviral efficacy against BA.2.75.2 and BQ.1.1, whereas Xevudy (Sotrovimab) remained weakly active. BQ.1.1 was also resistant to Bebtelovimab. Neutralizing titers in triply vaccinated individuals were low to undetectable against BQ.1.1 and BA.2.75.2, 4 months after boosting. A BA.1/BA.2 breakthrough infection increased these titers, which remained about 18-fold lower against BA.2.75.2 and BQ.1.1, than against BA.1. Reciprocally, a BA.5 breakthrough infection increased more efficiently neutralization against BA.5 and BQ.1.1 than against BA.2.75.2. Thus, the evolution trajectory of novel Omicron subvariants facilitated their spread in immunized populations and raises concerns about the efficacy of most currently available mAbs.

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Section: Discussionmentioning

confidence: 78%

Resistance of Omicron subvariants BA.2.75.2, BA.4.6 and BQ.1.1 to neutralizing antibodies

Planas

Bruel

Staropoli

et al. 2022

Preprint

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“…Omicron BA.2 is highly diversified after emergence and is the origin of other recently emerging Omicron subvariants. Although both BA.5 and BA.2.75 diversified from BA.2, these two Omicron subvariants are phylogenetically independent to each other, suggesting that these two variants emerged independently 2 . However, recent studies including ours have demonstrated that the spike (S) proteins of these two variants exhibit similar evolutionary patterns: one is amino acid substitutions to evade antiviral humoral immunity, while the other is the substitution to increase the binding affinity to human angiotensin converting enzyme 2 (ACE2), the receptor for SARS-CoV-2 infection.…”

Section: Introductionmentioning

confidence: 96%

“…For BA.5, the F486V substitution contributes to evasion from antiviral humoral immunity [3][4][5][6] , while the L452R substitution increases ACE2 binding affinity 4,[7][8][9] . For BA.2.75, the G446S substitution is responsible for evasion from antiviral humoral immunity 6,[10][11][12][13][14] , while the N460K substitution increases ACE2 binding affinity 2,7,11 .…”

Section: Introductionmentioning

confidence: 99%

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Convergent evolution of the SARS-CoV-2 Omicron subvariants leading to the emergence of BQ.1.1 variant

Ito

Suzuki

Uriu

et al. 2022

Preprint

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115

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In late 2022, although the SARS-CoV-2 Omicron subvariants have highly diversified, some lineages have convergently acquired amino acid substitutions at five critical residues in the spike protein. Here, we illuminated the evolutionary rules underlying the convergent evolution of Omicron subvariants and the properties of one of the latest lineages of concern, BQ.1.1. Our phylogenetic and epidemic dynamics analyses suggest that Omicron subvariants independently increased their viral fitness by acquiring the convergent substitutions. Particularly, BQ.1.1, which harbors all five convergent substitutions, shows the highest fitness among the viruses investigated. Neutralization assays show that BQ.1.1 is more resistant to breakthrough BA.2/5 infection sera than BA.5. The BQ.1.1 spike exhibits enhanced binding affinity to human ACE2 receptor and greater fusogenicity than the BA.5 spike. However, the pathogenicity of BQ.1.1 in hamsters is comparable to or even lower than that of BA.5. Our multiscale investigations provide insights into the evolutionary trajectory of Omicron subvariants.

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“…In addition, BA.2 gave rise to the BA.2.75 subvariant, which is currently increasing in proportion of COVID-19 cases (Centers for Disease Control and Prevention, 2022), but does not exhibit as substantial immune escape compared to BA.4/5 (Cao et al, 2022a;Qu et al, 2022a;Saito et al;Wang et al, 2022c). The BA.4/5 and BA.2.75 subvariants have driven further diversification of the circulating SARS-CoV-2, with the emergence of several additional subvariants including the BA.4.6, BF.7, BQ.1, and BQ.1.1 (derived from BA.4/5), as well as BA.…”

Section: Introductionmentioning

confidence: 99%

Distinct Neutralizing Antibody Escape of SARS-CoV-2 Omicron Subvariants BQ.1, BQ.1.1, BA.4.6, BF.7 and BA.2.75.2

Evans

Faraone

et al. 2022

Preprint

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Continued evolution of SARS-CoV-2 has led to the emergence of several new Omicron subvariants including BQ.1, BQ.1.1, BA.4.6, BF.7 and BA.2.75.2. Here we examine the neutralization resistance of these subvariants as well as their ancestral BA.4/5, BA.2.75 and D614G variants against sera from 3-dose vaccinated health care workers, hospitalized BA.1-wave patients, and BA.5-wave patients. We found enhanced neutralization resistance in all new subvariants, especially the BQ.1 and BQ.1.1 subvariants driven by a key N460K mutation and to a lesser extent, R346T and K444T mutations, as well as the BA.2.75.2 subvariant driven largely by its key F486S mutation. The BQ.1 and BQ.1.1 subvariants also exhibited enhanced fusogenicity and S processing dictated by the key N460K mutation. Interestingly, the BA.2.75.2 subvariant saw an enhancement by the F486S mutation and a reduction by the D1199N mutation to its fusogenicity and S processing resulting in minimal overall change. Molecular modelling revealed the mechanisms of receptor-binding and non-receptor binding monoclonal antibody-mediated immune evasion by R346T, K444T, F486S and D1199N mutations. Altogether, these findings shed light on the concerning evolution of newly emerging SARS-CoV-2 Omicron subvariants.

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Virological characteristics of the SARS-CoV-2 Omicron BA.2.75 variant

Cited by 152 publications

References 86 publications

Resistance of Omicron subvariants BA.2.75.2, BA.4.6 and BQ.1.1 to neutralizing antibodies

Resistance of Omicron subvariants BA.2.75.2, BA.4.6 and BQ.1.1 to neutralizing antibodies

Convergent evolution of the SARS-CoV-2 Omicron subvariants leading to the emergence of BQ.1.1 variant

Distinct Neutralizing Antibody Escape of SARS-CoV-2 Omicron Subvariants BQ.1, BQ.1.1, BA.4.6, BF.7 and BA.2.75.2

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