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

Saito, Akatsuki; Tamura, Tomokazu; Zahradník, Jiří; Deguchi, Sayaka; Tabata, Koshiro; Kimura, Izumi; Ito, Jumpei; Nasser, Hesham; Toyoda, Mako; Nagata, Kayoko; Uriu, Keiya; Kosugi, Yusuke; Fujita, Shigeru; Yamasoba, Daichi; Shofa, Maya; Begum, MST Monira; Oda, Yoshitaka; Suzuki, Rigel; Ito, Hayato; Nao, Naganori; Wang, Lei; Tsuda, Masumi; Yoshimatsu, Kumiko; 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; Takayama, Kazuo; Matsuno, Keita; Tanaka, Shinya; Ikeda, Terumasa; Fukuhara, Takasuke; Sato, Kei

doi:10.1101/2022.08.07.503115

Cited by 22 publications

(43 citation statements)

References 93 publications

(325 reference statements)

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“…Limitations of this study include a relatively small sample size for the boosted health care workers and the utilization of pseudotyped lentivirus for the neutralization assay rather than an authentic virus assay. However, our results for neutralization resistance are in accordance with several recent preprints (Cao et al, 2022; Gruell et al, 2022; Saito et al, 2022; Sheward et al, 2022; Wang et al, 2022b; Xie et al, 2022; Yamasoba et al, 2022a). Additionally, the lentiviral psedotype neutralization assay has been previously validated by assays with authentic SARS-CoV-2 (Zeng et al, 2020), and confirmed by numerous laboratories in the field.…”

Section: Discussionsupporting

confidence: 93%

“…We further demonstrate that BA.2.75 exhibits enhanced S-mediated cell-cell fusion compared to BA.2, albeit to a lesser extent than BA.4/5. This enhanced triggering of BA.2.75 Smediated fusion may reflect improved receptor utilization that is not present in earlier Omicron subvariants, consistent with several recent preprints (Cao et al, 2022;Saito et al, 2022;Wang et al, 2022a). Critically, we find that the N460K mutation present in BA.2.75 is essential for the enhanced fusion phenotype.…”

Section: Discussionsupporting

confidence: 87%

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Evasion of Neutralizing Antibody Response by the SARS-CoV-2 BA.2.75 Variant

Evans

Zheng

et al. 2022

Preprint

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The newly emerged BA.2.75 SARS-CoV-2 variant exhibits an alarming 9 additional mutations in its spike (S) protein compared to the ancestral BA.2 variant. Here we examine the neutralizing antibody escape of BA.2.75 in mRNA-vaccinated and BA.1-infected individuals, as well as the molecular basis underlying functional changes in the S protein. Notably, BA.2.75 exhibits enhanced neutralization resistance over BA.2, but less than the BA.4/5 variant. The G446S and N460K mutations of BA.2.75 are primarily responsible for its enhanced resistance to neutralizing antibodies. The R493Q mutation, a reversion to the prototype sequence, reduces BA.2.75 neutralization resistance. The mutational impact is consistent with their locations in common neutralizing antibody epitopes. Further, the BA.2.75 variant shows enhanced cell-cell fusion over BA.2, driven largely by the N460K mutation, which enhances S processing. Structural modeling revealed a new receptor contact introduced by N460K, supporting a mechanism of potentiated receptor utilization and syncytia formation.

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Section: Discussionsupporting

confidence: 93%

Section: Discussionsupporting

confidence: 87%

Evasion of Neutralizing Antibody Response by the SARS-CoV-2 BA.2.75 Variant

Evans

Zheng

et al. 2022

Preprint

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“…The reason for this is unclear; however, it might be due to differences in the binding affinity of the S protein for hACE2 among BA.1, BA.2, BA.4, BA.5, and BA.2.75. Recent studies have reported that the RBD of BA.2.75 exhibits higher binding affinity for the hACE2 receptor than that of BA.2 and BA.4/5 (Cao et al, 2022;Saito et al, 2022). SARS-CoV-2 enters cells in two distinct ways: by fusion of the viral lipid envelope with the target cell plasma membrane or fusion of the viral envelope with the endosomal membrane after internalization through the endocytic pathway (Hoffmann et al, 2020;Jackson et al, 2022;Walls et al, 2020).…”

Section: Discussionmentioning

confidence: 99%

Characterization of SARS-CoV-2 Omicron BA.2.75 clinical isolates

Uraki

Iida

Halfmann

et al. 2022

Preprint

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The prevalence of the Omicron subvariant BA.2.75 is rapidly increasing in India and Nepal. In addition, BA.2.75 has been detected in at least 34 other countries and is spreading globally. However, the virological features of BA.2.75 are largely unknown. Here, we evaluated the replicative ability and pathogenicity of BA.2.75 clinical isolates in Syrian hamsters. Although we found no substantial differences in weight change among hamsters infected with BA.2, BA.5, or BA.2.75, the replicative ability of BA.2.75 in the lungs was higher than that of BA.2 and BA.5. Of note, BA.2.75 caused focal viral pneumonia in hamsters, characterized by patchy inflammation interspersed in alveolar regions, which was not observed in BA.5-infected hamsters. Moreover, in competition assays, BA.2.75 replicated better than BA.5 in the lungs of hamsters. These results suggest that BA.2.75 can cause more severe respiratory disease than BA.5 and BA.2 and should be closely monitored.

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“…Although our analysis of vaccinee sera was limited to a single post-booster timepoint, our results and those of others suggest that antibody escape is an overall less pronounced characteristic of BA.2.75 compared with BA.4/5. 7 , 8 , 9 Thus, additional features favouring viral expansion beyond vaccine escape might be required for BA.2.75 to gain a growth advantage over BA.4/5.…”

mentioning

confidence: 99%