Structural analysis of receptor binding domain mutations in SARS-CoV-2 variants of concern that modulate ACE2 and antibody binding

Article Multidisciplinary Sciences

A therapeutic neutralizing antibody targeting receptor binding domain of SARS-CoV-2 spike protein

Cheolmin Kim et al.

Summary: A human monoclonal antibody called CT-P59 has been shown to effectively neutralize SARS-CoV-2 and demonstrate significant therapeutic effects in animal models, making it a promising candidate for COVID-19 treatment.

NATURE COMMUNICATIONS (2021)

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Article Microbiology

Identification of SARS-CoV-2 spike mutations that attenuate monoclonal and serum antibody neutralization

Zhuoming Liu et al.

Summary: The study found that antibodies targeting the SARS-CoV-2 spike protein have escape mutations, different monoclonal antibodies have unique resistance profiles, some mutants are resistant to multiple antibodies while some variants can escape neutralization by convalescent sera. Comparing antibody-mediated mutations with circulating SARS-CoV-2 sequences revealed substitutions that may weaken neutralizing immune responses in some individuals, warranting further investigation.

CELL HOST & MICROBE (2021)

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Editorial Material Medicine, General & Internal

SARS-CoV-2 Vaccines and the Growing Threat of Viral Variants

John P. Moore et al.

Summary: This article reviews the circulating SARS-CoV-2 genetic variants and the mechanisms of immunity by which they may escape vaccine-induced protection, proposing 6 measures to address these issues, including enhanced variant isolation and testing procedures, and continued adherence to mask-wearing and other established public health measures.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2021)

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Article Multidisciplinary Sciences

Sensitivity of SARS-CoV-2 B.1.1.7 to mRNA vaccine-elicited antibodies

Dami A. Collier et al.

Summary: The B.1.1.7 variant of SARS-CoV-2 exhibited reduced neutralization by vaccines and antibodies from recovered COVID-19 patients, with a more substantial loss seen when introducing the E484K mutation. This mutation poses a threat to the efficacy of the BNT162b2 vaccine.

NATURE (2021)

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Article Multidisciplinary Sciences

Antibody resistance of SARS-CoV-2 variants B.1.351 and B.1.1.7

Pengfei Wang et al.

Summary: The COVID-19 pandemic has had global repercussions, with promising vaccines and monoclonal antibody therapies. However, newly detected variants of SARS-CoV-2 present challenges to these treatment options.

NATURE (2021)

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Article Multidisciplinary Sciences

mRNA vaccine-elicited antibodies to SARS-CoV-2 and circulating variants

Zijun Wang et al.

Summary: Volunteers who received the Moderna or Pfizer-BioNTech vaccine showed high levels of antibodies and memory B cell responses against SARS-CoV-2, with activity similar to individuals who had recovered from natural infection. However, their efficacy against specific SARS-CoV-2 variants was reduced, indicating a potential need for periodic updates to mRNA vaccines to maintain clinical efficacy.

NATURE (2021)

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Article Biochemistry & Molecular Biology

Resistance of SARS-CoV-2 variants to neutralization by monoclonal and serum-derived polyclonal antibodies

Rita E. Chen et al.

Summary: The study analyzed antibody neutralization activity against a panel of authentic isolates and chimeric SARS-CoV-2 variants, showing significantly reduced neutralizing activity against the B.1.351 variant first identified in South Africa. Antibodies targeting the receptor-binding domain and N-terminal domain, monoclonal antibodies, convalescent sera, and mRNA vaccine-induced immune sera exhibited decreased inhibitory activity against viruses with an E484K spike mutation, suggesting a need for updated monoclonal antibodies or vaccine adjustments to prevent loss of protection against emerging variants.

NATURE MEDICINE (2021)

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Article Biochemistry & Molecular Biology

SARS-CoV-2 501Y.V2 escapes neutralization by South African COVID-19 donor plasma

Constantinos Kurt Wibmer et al.

Summary: The SARS-CoV-2 virus in the B.1.351 variant discovered in South Africa can evade neutralization by most antibodies when expressed, but does not affect binding by convalescent plasma. This suggests the potential for reinfection with antigenically distinct variants and predicts reduced efficacy of spike-based vaccines.

NATURE MEDICINE (2021)

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Article Biochemistry & Molecular Biology

N-terminal domain antigenic mapping reveals a site of vulnerability for SARS-CoV-2

Matthew McCallum et al.

Summary: The study identifies 41 human monoclonal antibodies that recognize the N-terminal domain of the SARS-CoV-2 spike protein and exhibit strong neutralizing activity. These antibodies inhibit cell-to-cell fusion, activate effector functions, and protect animals from virus challenge, highlighting the importance of NTD-specific neutralizing antibodies for protective immunity and vaccine development. Several SARS-CoV-2 variants with mutations in the NTD supersite suggest ongoing selective pressure on the virus.

CELL (2021)

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Article Biochemistry & Molecular Biology

Transmission, infectivity, and neutralization of a spike L452R SARS-CoV-2 variant

Xianding Deng et al.

Summary: A new SARS-CoV-2 variant named B.1.427/B.1.429 was identified in California, with increased transmissibility and carrying three mutations in spike protein, including L452R substitution. The variant emerged in May 2020 and became predominant in sequenced cases from September 2020 to January 2021. In vivo viral shedding was increased and antibody neutralization decreased, calling for further investigation.

CELL (2021)

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Article Biochemistry & Molecular Biology

Antibody evasion by the P.1 strain of SARS-CoV-2

Wanwisa Dejnirattisai et al.

Summary: Ending the SARS-CoV-2 pandemic requires global vaccination. New virus strains with mutations impact antibody responses, but some variants are less resistant than others. A monoclonal antibody can neutralize different variants and partially restore neutralization potency for other public antibodies.

CELL (2021)

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Article Microbiology

Increased resistance of SARS-CoV-2 variant P.1 to antibody neutralization

Pengfei Wang et al.

Summary: The emerging Brazilian variant P.1 shows increased resistance to antibody neutralization, posing a threat to current antibody therapies, but has less impact on the effectiveness of protective vaccines.

CELL HOST & MICROBE (2021)

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Article Biochemistry & Molecular Biology

Cryo-electron microscopy structures of the N501Y SARS-CoV-2 spike protein in complex with ACE2 and 2 potent neutralizing antibodies

Xing Zhu et al.

Summary: The UK variant of SARS-CoV-2 with the N501Y mutation shows increased infectivity due to tighter binding with the ACE2 receptor, but without significant structural changes. Important neutralization epitopes in the spike receptor binding domain are retained.

PLOS BIOLOGY (2021)

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Article Immunology

Analysis of SARS-CoV-2 variant mutations reveals neutralization escape mechanisms and the ability to use ACE2 receptors from additional species

Ruoke Wang et al.

Summary: Research shows that the South African B.1.351 variant exhibits the highest resistance to current monoclonal antibodies and convalescent plasma from COVID-19-infected individuals, and the molecular basis for this resistance and potential antibody escape has been identified.

IMMUNITY (2021)

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Article Infectious Diseases

Structural dynamics of SARS-CoV-2 variants: A health monitoring strategy for anticipating Covid-19 outbreaks

Jacques Fantini et al.

Summary: This study aimed to predict the transmissibility of SARS-CoV-2 variants by analyzing genomic sequence data. The researchers found that the NTD and RBD domains of the spike protein synergistically affect virus adhesion, leading to mutations in both domains in most variants. They introduced a transmissibility index (T-index) based on the kinetic and affinity parameters of coronavirus binding to host cells, which can predict the dissemination of each variant in animal and human populations.

JOURNAL OF INFECTION (2021)

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Article Biochemistry & Molecular Biology

Experimental Evidence for Enhanced Receptor Binding by Rapidly Spreading SARS-CoV-2 Variants

Charlie Laffeber et al.

Summary: Different mutations in new variants of SARS-CoV-2 have varying effects on receptor binding affinity, viral transmission, and immune evasion, highlighting the importance of global viral genome surveillance and functional characterization.

JOURNAL OF MOLECULAR BIOLOGY (2021)

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Article Multidisciplinary Sciences

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

Meng Yuan et al.

Summary: Mutations in the RBS residues of new variant strains of the coronavirus can affect the binding and neutralizing effects of antibodies, but have little impact on antibodies targeting more conserved neutralizing sites.

SCIENCE (2021)

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Article Chemistry, Multidisciplinary

Molecular recognition of SARS-CoV-2 spike glycoprotein: quantum chemical hot spot and epitope analyses†

Chiduru Watanabe et al.

Summary: Due to the COVID-19 pandemic, researchers have been studying the interaction between SARS-CoV-2 spike glycoprotein and ACE2 or blocking antibodies in detail. Their findings have provided valuable insights into the key amino acid residues critical for molecular recognition, binding, and potential drug design against the virus. Through their analysis, researchers have identified novel hot spots and epitopes that were previously overlooked, which may contribute to future antibody design and evaluation of SARS-CoV-2 variants.

CHEMICAL SCIENCE (2021)

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Article Multidisciplinary Sciences

Cell entry mechanisms of SARS-CoV-2

Jian Shang et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2020)

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Article Multidisciplinary Sciences

A noncompeting pair of human neutralizing antibodies block COVID-19 virus binding to its receptor ACE2

Yan Wu et al.

SCIENCE (2020)

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Article Multidisciplinary Sciences

A human neutralizing antibody targets the receptor-binding site of SARS-CoV-2

Rui Shi et al.

NATURE (2020)

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Article Multidisciplinary Sciences

Human neutralizing antibodies elicited by SARS-CoV-2 infection

Bin Ju et al.

NATURE (2020)

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Article Multidisciplinary Sciences

Cross-neutralization ofSARS-CoV-2 by a human monoclonal SARS-CoV antibody

Dora Pinto et al.

NATURE (2020)

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Article Biochemistry & Molecular Biology

Structures of Human Antibodies Bound to SARS-CoV-2 Spike Reveal Common Epitopes and Recurrent Features of Antibodies

Christopher O. Barnes et al.

CELL (2020)

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Article Biochemistry & Molecular Biology

Potent Neutralizing Antibodies against SARS-CoV-2 Identified by High-Throughput Single-Cell Sequencing of Convalescent Patients' B Cells

Yunlong Cao et al.

CELL (2020)

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Article Biochemistry & Molecular Biology

Mapping Neutralizing and Immunodominant Sites on the SARS-CoV-2 Spike Receptor-Binding Domain by Structure-Guided High-Resolution Serology

Luca Piccoli et al.

CELL (2020)

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Article Biochemistry & Molecular Biology

High Potency of a Bivalent Human VH Domain in SARS-CoV-2 Animal Models

Wei Li et al.

CELL (2020)

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Potent neutralizing antibodies against multiple epitopes on SARS-CoV-2 spike

Lihong Liu et al.

NATURE (2020)

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Article Biochemistry & Molecular Biology

Structural basis for the neutralization of SARS-CoV-2 by an antibody from a convalescent patient

Daming Zhou et al.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2020)

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Engineering human ACE2 to optimize binding to the spike protein of SARS coronavirus 2

Kui K. Chan et al.

SCIENCE (2020)

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Structure-based design of prefusion-stabilized SARS-CoV-2 spikes

Ching-Lin Hsieh et al.

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Structural basis of a shared antibody response to SARS-CoV-2

Meng Yuan et al.

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SARS-CoV-2 vaccines in development

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SARS-CoV-2 neutralizing antibody structures inform therapeutic strategies

Christopher O. Barnes et al.

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Engineered ACE2 receptor traps potently neutralize SARS-CoV-2

Anum Glasgow et al.

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Ultrapotent human antibodies protect against SARS-CoV-2 challenge via multiple mechanisms

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An Alternative Binding Mode of IGHV3-53 Antibodies to the SARS-CoV-2 Receptor Binding Domain

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Rapid identification of a human antibody with high prophylactic and therapeutic efficacy in three animal models of SARS-CoV-2 infection

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Structural analysis of receptor binding domain mutations in SARS-CoV-2 variants of concern that modulate ACE2 and antibody binding

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