SARS-CoV-2 Variants of Concern and Variants of Interest Receptor Binding Domain Mutations and Virus Infectivity

Liu, Haolin; Wei, Pengcheng; Kappler, John W.; Marrack, Philippa; Zhang, Gongyi

doi:10.3389/fimmu.2022.825256

Cited by 63 publications

(67 citation statements)

References 42 publications

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“…The SARS-CoV-2 Omicron variant contains >30 mutations in the SARS-CoV-2 spike protein, allowing rapid spread around the globe, and resulting in large outbreaks in children and adolescents 1 – 6 . Studies in adults show the SARS-CoV-2 Omicron variant is resistant to neutralizing antibodies after a prior SARS-CoV-2 infection or current SARS-CoV-2 vaccines 2 , 7 – 9 .…”

Section: Introductionmentioning

confidence: 99%

Cross-reactive immunity against the SARS-CoV-2 Omicron variant is low in pediatric patients with prior COVID-19 or MIS-C

et al. 2022

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Neutralization capacity of antibodies against Omicron after a prior SARS-CoV-2 infection in children and adolescents is not well studied. Therefore, we evaluated virus-neutralizing capacity against SARS-CoV-2 Alpha, Beta, Gamma, Delta and Omicron variants by age-stratified analyses (<5, 5–11, 12–21 years) in 177 pediatric patients hospitalized with severe acute COVID-19, acute MIS-C, and in convalescent samples of outpatients with mild COVID-19 during 2020 and early 2021. Across all patients, less than 10% show neutralizing antibody titers against Omicron. Children <5 years of age hospitalized with severe acute COVID-19 have lower neutralizing antibodies to SARS-CoV-2 variants compared with patients >5 years of age. As expected, convalescent pediatric COVID-19 and MIS-C cohorts demonstrate higher neutralization titers than hospitalized acute COVID-19 patients. Overall, children and adolescents show some loss of cross-neutralization against all variants, with the most pronounced loss against Omicron. In contrast to SARS-CoV-2 infection, children vaccinated twice demonstrated higher titers against Alpha, Beta, Gamma, Delta and Omicron. These findings can influence transmission, re-infection and the clinical disease outcome from emerging SARS-CoV-2 variants and supports the need for vaccination in children.

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Section: Introductionmentioning

confidence: 99%

Cross-reactive immunity against the SARS-CoV-2 Omicron variant is low in pediatric patients with prior COVID-19 or MIS-C

et al. 2022

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“…Specific subsets of mutations have been associated with each variant of concern, when mutations were represented in a majority of sequenced samples of their lineage. Notably, a special focus has been given with regards to the impact of mutations occurring within the spike-encoding gene (50), owing its importance in the initial steps of viral infection and its potential for vaccine neutralization (31). However, due to a lack of appropriate methods, the impact of these mutations at the regulatory level, such as their impact on protein-RNA interactions, has so far been largely ignored.…”

Section: Resultsmentioning

confidence: 99%

Computational Mapping of the Human-SARS-CoV-2 Protein-RNA Interactome

Horlacher

Oleshko

et al. 2021

Preprint

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It is well known that viruses make extensive use of the host cell's machinery, hijacking it for the purpose of viral replication and interfere with the activity of master regulatory proteins - including RNA binding proteins (RBPs). RBPs recognize and bind RNA molecules to control several steps of cellular RNA metabolism, such as splicing, transcript stability, translation and others, and recognize their targets by means of sequence or structure motifs. Host RBPs are critical factors for viral replication, especially for RNA viruses, and have been shown to influence viral RNA stability, replication and escape of host immune response. While current research efforts have been centered around identifying mechanisms of host cell-entry, the role of host RBPs in the context of SARS-CoV-2 replication remains poorly understood. Few experimental studies have started mapping the SARS-CoV-2 RNA-protein interactome in infected human cells, but they are limited in the resolution and exhaustivity of their output. On the other hand, computational approaches enable screening of large numbers of human RBPs for putative interactions with the viral RNA, and are thus crucial to prioritize candidates for further experimental investigation. Here, we investigate the role of RBPs in the context of SARS-CoV-2 by constructing a first single-nucleotide \textit{in silico} map of human RBP / viral RNA interactions by using deep learning models trained on RNA sequences. Our framework is based on Pysster and DeepRiPe, two deep learning method which use a convolutional neural network to learn sequence-structure preferences of a specific RBP. Models were trained using eCLIP and PAR-CLIP datasets for >150 RBP generated on human cell lines and applied cross-species to predict the propensity of each RBP to bind the SARS-CoV-2 genome. After extensive validation of predicted binding sites, we generate RBP binding profiles across different SARS-CoV-2 variants and 6 other betacoronaviruses. We address the questions of (1) conservation of binding between pathogenic betacoronaviruses, (2) differential binding across viral strains and (3) gain and loss of binding events in novel mutants which can be linked to disease severity and spread in the population. In addition, we explore the specific pathways hijacked by the virus, by integrating host factors linked to these virus-binding RBPs through protein-protein interaction networks or genome wide CRISPR screening. We believe that identifying viral RBP binding sites will give valuable insights into the mechanisms of host-virus interaction, thus giving us a deeper understanding of the life cycle of SARS-CoV-2 but also opening new avenues for the development of new therapeutics.

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“…Concerns over the evolution of viral variants prompted calls to perform wholegenome sequencing on SARS-CoV-2 genomes to catalog and track their lineages. To date, the most significant variants of concern (VOCs) are Alpha (B.1.1.7), Beta (B.1.351), Iota (B.1.526), Gamma (P.1), Delta (B.1.617.2) and most recently, Omicron (B.1.1.529, BA.1, BA.2, or BA.3), primarily due to their increased infectivity [2][3][4][5] , higher viral load 6 , or potential for immune evasion 7,8 .…”

Section: Introductionmentioning

confidence: 99%

“…Concerns over the evolution of viral variants prompted calls to perform whole-genome sequencing on SARS-CoV-2 genomes to catalog and track their lineages. To date, the most significant variants of concern (VOCs) are Alpha (B.1.1.7), Beta (B.1.351), Iota (B.1.526), Gamma (P.1), Delta (B.1.617.2) and most recently, Omicron (B.1.1.529, BA.1, BA.2, or BA.3), primarily due to their increased infectivity 2–5 , higher viral load 6 , or potential for immune evasion 7,8 . To understand the changing dynamics of VOC proliferation in NYC, a citywide genomic biosurveillance system was proposed to track the emergence and spread of VOCs for the purpose of informing policy decisions and implementing public health countermeasures.…”

Section: Introductionmentioning

confidence: 99%

Development and scaling of a sequencing pipeline for genomic surveillance of SARS-CoV-2 in New York City

Hammerling¹,

Kang²,

Ward³

et al. 2022

Preprint

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In the ongoing COVID-19 pandemic, detecting the appearance and spread of variants of concern (VOC) is a critical capability in the fight to quell the virus and return to normalcy. Genomic surveillance of the emergence, propagation, and geographical spread of VOCs is thus an important tool for public health officials and government leaders to make policy decisions and advise the public. As part of our role as a major SARS-CoV-2 diagnostic testing facility in New York City, the Pandemic Response Lab (PRL) has been performing genomic surveillance on the large number of positive samples processed by the facility on a daily basis from throughout the New York metropolitan area. Here we describe the development and optimization of a high-throughput SARS-CoV-2 genome sequencing facility at PRL serving New York City.

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SARS-CoV-2 Variants of Concern and Variants of Interest Receptor Binding Domain Mutations and Virus Infectivity

Cited by 63 publications

References 42 publications

Cross-reactive immunity against the SARS-CoV-2 Omicron variant is low in pediatric patients with prior COVID-19 or MIS-C

Cross-reactive immunity against the SARS-CoV-2 Omicron variant is low in pediatric patients with prior COVID-19 or MIS-C

Computational Mapping of the Human-SARS-CoV-2 Protein-RNA Interactome

Development and scaling of a sequencing pipeline for genomic surveillance of SARS-CoV-2 in New York City

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