SARS-CoV-2 Omicron-B.1.1.529 leads to widespread escape from neutralizing antibody responses

Cell, Journal Year: 2022, Volume and Issue: 185(3), P. 467 - 484.e15

Published: Jan. 4, 2022

On 24th November 2021, the sequence of a new SARS-CoV-2 viral isolate Omicron-B.1.1.529 was announced, containing far more mutations in Spike (S) than previously reported variants. Neutralization titers Omicron by sera from vaccinees and convalescent subjects infected with early pandemic Alpha, Beta, Gamma, or Delta are substantially reduced, failed to neutralize. Titers against boosted third vaccine doses high both vaccinated individuals those Delta. Mutations knock out reduce neutralization most large panel potent monoclonal antibodies under commercial development. S has structural changes earlier viruses uses that confer tight binding ACE2 unleash evolution driven immune escape. This leads number site rebalances receptor affinity viruses.

Language: Английский

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The evolution of SARS-CoV-2

Nature Reviews Microbiology, Journal Year: 2023, Volume and Issue: 21(6), P. 361 - 379

Published: April 5, 2023

Language: Английский

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Long COVID or Post-acute Sequelae of COVID-19 (PASC): An Overview of Biological Factors That May Contribute to Persistent Symptoms

Frontiers in Microbiology, Journal Year: 2021, Volume and Issue: 12

Published: June 23, 2021

The novel virus severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has caused a pandemic of disease 2019 (COVID-19). Across the globe, subset patients who sustain an SARS-CoV-2 infection are developing wide range persistent symptoms that do not resolve over course many months. These being given diagnosis Long COVID or Post-acute sequelae COVID-19 (PASC). It is likely individual with PASC have different underlying biological factors driving their symptoms, none which mutually exclusive. This paper details mechanisms by RNA viruses beyond just be connected to long-term health consequences. also reviews literature on and other virus-initiated chronic syndromes such as post-Ebola myalgic encephalomyelitis/chronic fatigue (ME/CFS) discuss scenarios for symptom development. Potential contributors include consequences from injury one multiple organs, reservoirs in certain tissues, re-activation neurotrophic pathogens herpesviruses under conditions immune dysregulation, interactions host microbiome/virome communities, clotting/coagulation issues, dysfunctional brainstem/vagus nerve signaling, ongoing activity primed cells, autoimmunity due molecular mimicry between pathogen proteins. individualized nature suggests therapeutic approaches may required best manage care specific diagnosis.

Language: Английский

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Antibody escape of SARS-CoV-2 Omicron BA.4 and BA.5 from vaccine and BA.1 serum

Cell, Journal Year: 2022, Volume and Issue: 185(14), P. 2422 - 2433.e13

Published: June 9, 2022

The Omicron lineage of SARS-CoV-2, which was first described in November 2021, spread rapidly to become globally dominant and has split into a number sublineages. BA.1 dominated the initial wave but been replaced by BA.2 many countries. Recent sequencing from South Africa's Gauteng region uncovered two new sublineages, BA.4 BA.5, are taking over locally, driving wave. BA.5 contain identical spike sequences, although closely related BA.2, they further mutations receptor-binding domain their spikes. Here, we study neutralization BA.4/5 using range vaccine naturally immune serum panels monoclonal antibodies. shows reduced individuals vaccinated with triple doses AstraZeneca or Pfizer compared BA.2. Furthermore, breakthrough infections, there are, likewise, significant reductions BA.4/5, raising possibility repeat infections.

Language: Английский

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Receptor binding and complex structures of human ACE2 to spike RBD from omicron and delta SARS-CoV-2

Cell, Journal Year: 2022, Volume and Issue: 185(4), P. 630 - 640.e10

Published: Jan. 6, 2022

Language: Английский

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

Cell, Journal Year: 2022, Volume and Issue: 185(5), P. 860 - 871.e13

Published: Jan. 25, 2022

The SARS-CoV-2 Omicron variant with increased fitness is spreading rapidly worldwide. Analysis of cryo-EM structures the spike (S) from reveals amino acid substitutions forging interactions that stably maintain an active conformation for receptor recognition. relatively more compact domain organization confers improved stability and enhances attachment but compromises efficiency viral fusion step. Alterations in local conformation, charge, hydrophobic microenvironments underpin modulation epitopes such they are not recognized by most NTD- RBD-antibodies, facilitating immune escape. Structure S bound human ACE2, together analysis sequence conservation ACE2 binding region 25 sarbecovirus members, as well heatmaps immunogenic sites their corresponding mutational frequencies, sheds light on conserved structurally restrained regions can be used development broad-spectrum vaccines therapeutics.

Language: Английский

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Neutralization of Severe Acute Respiratory Syndrome Coronavirus 2 Omicron Variant by Sera From BNT162b2 or CoronaVac Vaccine Recipients

Clinical Infectious Diseases, Journal Year: 2021, Volume and Issue: 75(1), P. e822 - e826

Published: Dec. 15, 2021

Abstract Background The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) omicron variant, designated as a variant of concern by the World Health Organization, carries numerous spike mutations that are known to evade neutralizing antibodies elicited disease 2019 (COVID-19) vaccines. A deeper understanding susceptibility vaccine-induced is urgently needed for risk assessment. Methods Omicron strains HKU691 and HKU344-R346K were isolated from patients using TMPRSS2-overexpressing VeroE6 cells. Whole genome sequence was determined nanopore sequencing. Neutralization ancestral lineage virus omicron, delta beta variants sera 25 BNT162b2 CoronaVac vaccine recipients live microneutralization assay. Results strain has an additional R346K mutation, which present in 8.5% deposited GISAID database. Only 20% 24% had detectable antibody against HKU344-R346K, respectively, whereas none titer either isolate. For recipients, geometric mean neutralization titers (GMTs) isolates (5.43 6.42) 35.7–39.9-fold lower than (229.4), GMTs both significantly those variants. There no significant difference between HKU344-R346K. Conclusions escapes or CoronaVac. mutation did not affect susceptibility. Our data suggest may be associated with COVID-19 effectiveness.

Language: Английский

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Structural and functional ramifications of antigenic drift in recent SARS-CoV-2 variants

Science, Journal Year: 2021, Volume and Issue: 373(6556), P. 818 - 823

Published: May 21, 2021

Neutralizing antibodies (nAbs) elicited against the receptor binding site (RBS) of spike protein wild-type severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) are generally less effective recent variants concern. RBS residues Glu

Language: Английский

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De novo emergence of a remdesivir resistance mutation during treatment of persistent SARS-CoV-2 infection in an immunocompromised patient: a case report

Nature Communications, Journal Year: 2022, Volume and Issue: 13(1)

Published: March 17, 2022

Abstract SARS-CoV-2 remdesivir resistance mutations have been generated in vitro but not reported patients receiving treatment with the antiviral agent. We present a case of an immunocompromised patient acquired B-cell deficiency who developed indolent, protracted course infection. Remdesivir therapy alleviated symptoms and produced transient virologic response, her was complicated by recrudescence high-grade viral shedding. Whole genome sequencing identified mutation, E802D, nsp12 RNA-dependent RNA polymerase, which pre-treatment specimens. In experiments demonstrated that mutation conferred ~6-fold increase IC 50 resulted fitness cost absence remdesivir. Sustained clinical response achieved after casirivimab-imdevimab. Although observed may limit risk posed this illustrates importance monitoring for potential benefit combinatorial therapies

Language: Английский

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Monoclonal antibodies for COVID-19 therapy and SARS-CoV-2 detection

Journal of Biomedical Science, Journal Year: 2022, Volume and Issue: 29(1)

Published: Jan. 4, 2022

The coronavirus disease 2019 (COVID-19) pandemic is an exceptional public health crisis that demands the timely creation of new therapeutics and viral detection. Owing to their high specificity reliability, monoclonal antibodies (mAbs) have emerged as powerful tools treat detect numerous diseases. Hence, many researchers begun urgently develop Ab-based kits for detection severe acute respiratory syndrome 2 (SARS-CoV-2) Ab drugs use COVID-19 therapeutic agents. detailed structure SARS-CoV-2 spike protein known, since this key infection, its receptor-binding domain (RBD) has become a major target development. Because RNA virus with mutation rate, especially under selective pressure aggressively deployed prophylactic vaccines neutralizing Abs, cocktails expected be important strategy effective treatment. Moreover, infection may stimulate overactive immune response, resulting in cytokine storm drives progression. Abs combat storms also been intense development treatments COVID-19. In addition drugs, are currently being utilized tests, including antigen immunoglobulin tests. Such tests crucial surveillance can used prevent spread Herein, we highlight some points regarding mAb-based pandemic.

Language: Английский

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