Structural and functional characterizations of infectivity and immune evasion of SARS-CoV-2 Omicron

Cui, Zhen; Liu, Pan; Wang, Nan; Wang, Lei; Fan, Kaiyue; Zhu, Qianhui; Wang, Kang; Chen, Ruihong; Feng, Rui; Jia, Zhimin; Yang, Mu; Xu, Ge; Zhu, Boling; Fu, Wangyang; Chu, Tianming; Feng, Leilei; Wang, Yide; Pei, Xinran; Yang, Peng; Xie, X. Sunney; Cao, Lei; Cao, Yunlong; Wang, Xiangxi

doi:10.1016/j.cell.2022.01.019

Cited by 366 publications

(453 citation statements)

References 62 publications

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“… 55 Additional mutations found in the Omicron variant (e.g., A67V, T95I, G142‐/V143‐/Y144‐/Y145D, and N211‐/L212I) are associated with infectious capacity, but their precise role remains to be elucidated. 56 …”

Section: Epidemiology and Features Of The Omicron Variantmentioning

confidence: 99%

SARS‐CoV‐2 Omicron variant: Immune escape and vaccine development

Lan

et al. 2022

MedComm

109

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New genetic variants of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) constantly emerge through unmitigated spread of the virus in the ongoing Coronavirus disease 2019 pandemic. Omicron (B.1.1.529), the latest variant of concern (VOC), has so far shown exceptional spread and infectivity and has established itself as the dominant variant in recent months. The SARS‐CoV‐2 spike glycoprotein is a key component for the recognition and binding to host cell angiotensin‐converting enzyme 2 receptors. The Omicron variant harbors a cluster of substitutions/deletions/insertions, and more than 30 mutations are located in spike. Some noticeable mutations, including K417N, T478K, N501Y, and P681H, are shared with the previous VOCs Alpha, Beta, Gamma, or Delta variants and have been proven to be associated with higher transmissibility, viral infectivity, and immune evasion potential. Studies have revealed that the Omicron variant is partially resistant to the neutralizing activity of therapeutic antibodies and convalescent sera, which poses significant challenges for the clinical effectiveness of the current vaccines and therapeutic antibodies. We provide a comprehensive analysis and summary of the epidemiology and immune escape mechanisms of the Omicron variant. We also suggest some therapeutic strategies against the Omicron variant. This review, therefore, aims to provide information for further research efforts to prevent and contain the impact of new VOCs during the ongoing pandemic.

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Section: Epidemiology and Features Of The Omicron Variantmentioning

confidence: 99%

SARS‐CoV‐2 Omicron variant: Immune escape and vaccine development

Lan

et al. 2022

MedComm

109

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“…Omicron variants is divided into three lineages (BA.1, BA.2, and BA. 3) and was classified as the fifth variant of concern (VOC) by the World Health Organization on November 26, 2021. It has been circulating in more than 170 countries/territories.…”

Section: Introductionmentioning

confidence: 99%

“…Previous research on Alpha (B.1.1.7) and Delta (B.1.617.2 and AY.x) variants with spike gene mutations confirmed these effects on enhancing virus transmission [4][5][6][7][8] . Meanwhile, as a critical antigenic recognition site, the spike protein is also the principal vaccine design target, and these observed mutations have focused attention on this modified antigen and its putative immune escape potential and antibody resistance 3,[10][11][12] .…”

Section: Introductionmentioning

confidence: 99%

Tracking SARS-CoV-2 Omicron diverse spike gene mutations identifies multiple inter-variant recombination events

Lan

et al. 2022

Preprint

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The current pandemic of COVID-19 is fueled by more infectious emergent Omicron variants. Ongoing concerns of emergent variants include possible recombinants, as genome recombination is an important evolutionary mechanism for the emergence and re-emergence of human viral pathogens. Although recombination events among SARS-CoV-1 and MERS-CoV were well-documented, it has been difficult to detect the recombination signatures in SARS-CoV-2 variants due to their high degree of sequence similarity. In this study, we identified diverse recombination events between two Omicron major subvariants (BA.1 and BA.2) and other variants of concern (VOCs) and variants of interest (VOIs), suggesting that co-infection and subsequent genome recombination play important roles in the ongoing evolution of SARS-CoV-2. Through scanning high-quality completed Omicron spike gene sequences, eighteen core mutations of BA.1 variants (frequency >99%) were identified (eight in NTD, five near the S1/S2 cleavage site, and five in S2). BA.2 variants share three additional amino acid deletions with the Alpha variants. BA.1 subvariants share nine common amino acid mutations (three more than BA.2) in the spike protein with most VOCs, suggesting a possible recombination origin of Omicron from these VOCs. There are three more Alpha-related mutations (del69-70, del144) in BA.1 than BA.2, and therefore BA.1 may be phylogenetically closer to the Alpha variant. Revertant mutations are found in some dominant mutations (frequency >95%) in the BA.1 subvariant. Most notably, multiple additional amino acid mutations in the Delta spike protein were also identified in the recently emerged Omicron isolates, which implied possible recombination events occurred between the Omicron and Delta variants during the on-going pandemic. Monitoring the evolving SARS-CoV-2 genomes especially for recombination is critically important for recognition of abrupt changes to viral attributes including its epitopes which may call for vaccine modifications.

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“…The Omicron variant harbors over 60 mutations, and 15 of the mutations are located in the receptor-binding domain (RBD). 1 Compared with parental virus and previous variants, the Omicron variant is characterized by decreased hospitalization rates and less severe disease in patients. 2 However, how the Omicron variant reduces pathogenicity remains unclear.…”

mentioning

confidence: 99%