Mechanisms of SARS-CoV-2 entry into cells

Nature Reviews Molecular Cell Biology, Journal Year: 2021, Volume and Issue: 23(1), P. 3 - 20

Published: Oct. 5, 2021

Language: Английский

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The biological and clinical significance of emerging SARS-CoV-2 variants

Nature Reviews Genetics, Journal Year: 2021, Volume and Issue: 22(12), P. 757 - 773

Published: Sept. 17, 2021

Language: Английский

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Reduced neutralization of SARS-CoV-2 B.1.617 by vaccine and convalescent serum

Cell, Journal Year: 2021, Volume and Issue: 184(16), P. 4220 - 4236.e13

Published: June 17, 2021

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has undergone progressive change, with variants conferring advantage rapidly becoming dominant lineages, e.g., B.1.617. With apparent increased transmissibility, variant B.1.617.2 contributed to the current wave of infection ravaging Indian subcontinent and been designated a concern in United Kingdom. Here we study ability monoclonal antibodies convalescent vaccine sera neutralize B.1.617.1 B.1.617.2, complement this structural analyses Fab/receptor binding domain (RBD) complexes, map antigenic space variants. Neutralization both viruses is reduced compared ancestral Wuhan-related strains, but there no evidence widespread antibody escape as seen B.1.351. However, B.1.351 P.1 showed markedly more reduction neutralization suggesting that individuals infected previously by these may be susceptible reinfection B.1.617.2. This observation provides important new insights for immunization policy future vaccines non-immune populations.

Language: Английский

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Omicron Variant (B.1.1.529): Infectivity, Vaccine Breakthrough, and Antibody Resistance

Journal of Chemical Information and Modeling, Journal Year: 2022, Volume and Issue: 62(2), P. 412 - 422

Published: Jan. 6, 2022

The latest severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) variant Omicron (B.1.1.529) has ushered panic responses around the world due to its contagious and vaccine escape mutations. essential infectivity antibody resistance of SARS-CoV-2 are determined by mutations on spike (S) protein receptor-binding domain (RBD). However, a complete experimental evaluation might take weeks or even months. Here, we present comprehensive quantitative analysis Omicron's infectivity, breakthrough, resistance. An artificial intelligence (AI) model, which been trained with tens thousands data extensively validated results SARS-CoV-2, reveals that may be over 10 times more than original virus about 2.8 as infectious Delta variant. On basis 185 three-dimensional (3D) structures antibody-RBD complexes, unveil have an 88% likelihood current vaccines. U.S. Food Drug Administration (FDA)-approved monoclonal antibodies (mAbs) from Eli Lilly seriously compromised. also diminish efficacy mAbs AstraZeneca, Regeneron mAb cocktail, Celltrion, Rockefeller University. impacts GlaxoSmithKline's sotrovimab appear mild. Our work calls for new strategies develop next generation mutation-proof vaccines antibodies.

Language: Английский

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SARS-CoV-2 Spike Mutations, L452R, T478K, E484Q and P681R, in the Second Wave of COVID-19 in Maharashtra, India

Microorganisms, Journal Year: 2021, Volume and Issue: 9(7), P. 1542 - 1542

Published: July 20, 2021

As the global severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic expands, genomic epidemiology and whole genome sequencing are being used to investigate its transmission evolution. Against backdrop of emergence "variants concern" (VOCs) during December 2020 an upsurge in a state western part India since January 2021, analysis spike protein mutations using sequence structural approaches were undertaken identify possible new variants gauge fitness current circulating strains. Phylogenetic revealed that newly identified lineages B.1.617.1 B.1.617.2 predominantly circulating. The signature possessed by these strains L452R, T478K, E484Q, D614G P681R protein, including within receptor-binding domain (RBD). Of these, at residue positions 452, 484 681 have been reported other globally lineages. RBD T478K E484Q may possibly result increased ACE2 binding while furin cleavage site could increase rate S1-S2 cleavage, resulting better transmissibility. two mutations, L452R indicated decreased select monoclonal antibodies (mAbs) affect their neutralization potential. Further vitro/in vivo studies would help confirm phenotypic changes mutant Overall, study emerged responsible for second wave COVID-19 Maharashtra. Lineage has designated as VOC delta variant interest kappa, they widely rest country well globally. Continuous monitoring emerging is essential.

Language: Английский

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Impact of SARS-CoV-2 variants on the total CD4+ and CD8+ T cell reactivity in infected or vaccinated individuals

Cell Reports Medicine, Journal Year: 2021, Volume and Issue: 2(7), P. 100355 - 100355

Published: July 1, 2021

The emergence of SARS-CoV-2 variants with evidence antibody escape highlight the importance addressing whether total CD4

Language: Английский

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SARS-CoV-2 spike L452R variant evades cellular immunity and increases infectivity

Cell Host & Microbe, Journal Year: 2021, Volume and Issue: 29(7), P. 1124 - 1136.e11

Published: June 15, 2021

Many SARS-CoV-2 variants with naturally acquired mutations have emerged. These can affect viral properties such as infectivity and immune resistance. Although the sensitivity of occurring to humoral immunity has been investigated, human leukocyte antigen (HLA)-restricted cellular remains largely unexplored. Here, we demonstrate that two recently emerging in receptor-binding domain spike protein, L452R (in B.1.427/429 B.1.617) Y453F B.1.1.298), confer escape from HLA-A24-restricted immunity. reinforce affinity toward host entry receptor ACE2. Notably, mutation increases stability, infectivity, fusogenicity, thereby promotes replication. data suggest HLA-restricted potentially affects evolution phenotypes a further threat pandemic is

Language: Английский

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SARS-CoV-2 immune evasion by the B.1.427/B.1.429 variant of concern

Science, Journal Year: 2021, Volume and Issue: 373(6555), P. 648 - 654

Published: July 1, 2021

A novel variant of concern (VOC) named CAL.20C (B.1.427/B.1.429), which was originally detected in California, carries spike glycoprotein mutations S13I the signal peptide, W152C N-terminal domain (NTD), and L452R receptor-binding (RBD). Plasma from individuals vaccinated with a Wuhan-1 isolate-based messenger RNA vaccine or convalescent exhibited neutralizing titers that were reduced 2- to 3.5-fold against B.1.427/B.1.429 relative wild-type pseudoviruses. The mutation activity 14 34 RBD-specific monoclonal antibodies (mAbs). resulted total loss neutralization for 10 NTD-specific mAbs because NTD antigenic supersite remodeled by shift peptide cleavage site formation new disulfide bond, as revealed mass spectrometry structural studies.

Language: Английский

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Mapping mutations to the SARS-CoV-2 RBD that escape binding by different classes of antibodies

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: July 7, 2021

Monoclonal antibodies targeting a variety of epitopes have been isolated from individuals previously infected with SARS-CoV-2, but the relative contributions these different antibody classes to polyclonal response remains unclear. Here we use yeast-display system map all mutations viral spike receptor-binding domain (RBD) that escape binding by representatives three potently neutralizing anti-RBD high-resolution structures. We compare antibody-escape maps similar for convalescent plasmas, including plasmas whom some were isolated. While plasma are affected across multiple RBD epitopes, plasma-escape most resemble those single class target an epitope on includes site E484. Therefore, although human immune can produce diverse in practice infection is skewed towards already undergoing rapid evolution.

Language: Английский

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Tackling COVID-19 with neutralizing monoclonal antibodies

Cell, Journal Year: 2021, Volume and Issue: 184(12), P. 3086 - 3108

Published: May 26, 2021

Language: Английский

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