4.7 Article

High-throughput screening of spike variants uncovers the key residues that alter the affinity and antigenicity of SARS-CoV-2

Related references

Note: Only part of the references are listed.
Article Biochemistry & Molecular Biology

A pseudovirus system enables deep mutational scanning of the full SARS-CoV-2 spike

Bernadeta Dadonaite et al.

Summary: This study describes a deep mutational scanning platform to understand the impact of emerging mutations in the spike protein of SARS-CoV-2 on antibody neutralization and pseudovirus infection. The platform can be extended to study entry proteins of other viruses.
Review Microbiology

SARS-CoV-2 variant evasion of monoclonal antibodies based on in vitro studies

MacGregor Cox et al.

Summary: Monoclonal antibodies (mAbs) are an important treatment option for severe COVID-19, but the emergence of new SARS-CoV-2 variants has led to evasion of mAb-induced protection. Spike protein amino acid substitutions, both at epitope and non-epitope positions, play a role in resistance to mAb neutralization. Understanding the dynamics of viral evasion can inform surveillance and the development of novel mAb therapies.

NATURE REVIEWS MICROBIOLOGY (2023)

Article Biochemistry & Molecular Biology

Disulfide Bonds Play a Critical Role in the Structure and Function of the Receptor-binding Domain of the SARS-CoV-2 Spike Antigen

Andrey M. Grishin et al.

Summary: The study found that the disulfide bonds of the SARSCoV-2 Spike receptor-binding domain (RBD) play a crucial role in cell receptor binding and viral internalization. Reduction of the four disulfide bonds in the RBD increases flexibility of surface loops, affecting its binding affinity to the ACE2 cell receptor and viral replication.

JOURNAL OF MOLECULAR BIOLOGY (2022)

Article Multidisciplinary Sciences

Omicron escapes the majority of existing SARS-CoV-2 neutralizing antibodies

Yunlong Cao et al.

Summary: The Omicron variant of SARS-CoV-2 contains 15 mutations in the receptor-binding domain, leading to evasion of over 85% of tested neutralizing antibodies. Different epitope groups of neutralizing antibodies are affected to varying degrees by single mutations of Omicron. Antibodies targeting the conserved region of sarbecovirus remain most effective against Omicron.

NATURE (2022)

Review Cell Biology

Mechanisms of SARS-CoV-2 entry into cells

Cody B. Jackson et al.

Summary: The entry of SARS-CoV-2 into host cells is facilitated by the interaction between the viral spike protein and ACE2, leading to virus-cell membrane fusion, which has been extensively studied at the structural and cellular levels worldwide. This understanding has paved the way for the development of effective vaccines in response to the COVID-19 pandemic, caused by the infection with SARS-CoV-2.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2022)

Review Chemistry, Multidisciplinary

Severe Acute Respiratory Syndrome Type 2-Causing Coronavirus: Variants and Preventive Strategies

Mehmet Onur Aydogdu et al.

Summary: COVID-19 vaccines have made a substantial scientific leap in countering the SARS-CoV-2 virus, and global vaccination programs have played a significant role in saving lives. However, the continuous evolution of the virus has resulted in different variants, some of which pose a threat to vaccine efficacy. This review highlights the significant variants of SARS-CoV-2 encountered so far and discusses preventive strategies, with a focus on physical and materials science.

ADVANCED SCIENCE (2022)

Article Biochemistry & Molecular Biology

Circular RNA vaccines against SARS-CoV-2 and emerging variants

Liang Qu et al.

Summary: This study reports a circular RNA vaccine that provides potent protection against SARS-CoV-2 by eliciting neutralizing antibodies and T cell responses. The circRNA vaccine exhibits higher and more durable antigen production compared to mRNA vaccines and shows efficacy against the current variants of concern.
Article Biochemistry & Molecular Biology

Protective prototype-Beta and Delta-Omicron chimeric RBD-dimer vaccines against SARS-CoV-2

Kun Xu et al.

Summary: A chimeric RBD-dimer vaccine approach was developed to adapt to SARS-CoV-2 variants, providing broader neutralization and better protection against different strains in animal models. This approach is applicable for rapid immunogen updating and could be used to combat circulating and emerging SARS-CoV-2 variants.
Review Biochemistry & Molecular Biology

The spike glycoprotein of SARS-CoV-2: A review of how mutations of spike glycoproteins have driven the emergence of variants with high transmissibility and immune escape

Pedro F. N. Souza et al.

Summary: This article discusses the mutations of SARS-CoV-2 and how these mutations have led to the emergence of new variants that are more transmissible and aggressive. The crucial role of the S protein in SARS-CoV-2 infection and evolution is explored, along with the impact of mutations on its functions.

INTERNATIONAL JOURNAL OF BIOLOGICAL MACROMOLECULES (2022)

Article Multidisciplinary Sciences

Transmission of SARS-CoV-2 from humans to animals and potential host adaptation

Cedric C. S. Tan et al.

Summary: The spread of SARS-CoV-2 in mink and deer did not require significant adaptation, resulted in moderate changes to the virus's evolutionary trajectory, and has not led to viral mutations that greatly improve human transmission thus far.

NATURE COMMUNICATIONS (2022)

Article Immunology

ACE2 decoy receptor generated by high-throughput saturation mutagenesis efficiently neutralizes SARS-CoV-2 and its prevalent variants

Bolun Wang et al.

Summary: This study reveals the impact of ACE2-PD point mutations on RBD-ACE2 binding and constructs an ACE2 decoy receptor named C4-1, which shows strong neutralization and binding affinity against SARS-CoV-2 and its variants, as well as inhibiting viral immune-escaping.

EMERGING MICROBES & INFECTIONS (2022)

Article Multidisciplinary Sciences

A live attenuated virus-based intranasal COVID-19 vaccine provides rapid, prolonged, and broad protection against SARS-CoV-2

Junyu Chen et al.

Summary: Significant progress has been made in the development of intramuscular vaccines against SARS-CoV-2, but they have limitations in eliciting local immunity in the respiratory tract. To overcome this, researchers have constructed a nasal vaccine candidate using an influenza vector that contains the receptor-binding domain (RBD) of the SARS-CoV-2 spike protein. Preclinical studies have shown that this vaccine candidate provides protection against lung pathology and demonstrates cross-protection against SARS-CoV-2 variants and other influenza viruses.

SCIENCE BULLETIN (2022)

Article Multidisciplinary Sciences

Probing the biophysical constraints of SARS-CoV-2 spike N-terminal domain using deep mutational scanning

Wenhao O. Ouyang et al.

Summary: In this study, the effects of NTD single mutations on S protein expression were quantified, revealing an inverse correlation between mutational tolerability of NTD residues and their proximity to RBD and S2. NTD mutations at the interdomain interface were also identified, which increased S protein expression without altering its antigenicity. This study advances the understanding of NTD's biophysical constraints and provides valuable insights into S-based immunogen design.

SCIENCE ADVANCES (2022)

Article Multidisciplinary Sciences

Shifting mutational constraints in the SARS-CoV-2 receptor-binding domain during viral evolution

Tyler N. Starr et al.

Summary: This study investigates the impact of mutations in the spike receptor-binding domain (RBD) of SARS-CoV-2 on its affinity for the ACE2 receptor and antibody recognition, as well as their implications for future evolution and interaction. The findings reveal that certain mutations cause shifts in the effects of mutations at other sites, shaping the evolutionary path of the virus.

SCIENCE (2022)

Article Microbiology

SARS-CoV-2 Omicron is an immune escape variant with an altered cell entry pathway

Brian J. Willett et al.

Summary: Vaccines based on the spike protein of SARS-CoV-2 are vital in combating COVID-19, but the emergence of the Omicron variant poses a threat to this strategy. Studies have shown that the Omicron variant evades neutralization by sera from individuals vaccinated with different vaccines and reduces real-world vaccine effectiveness, although booster vaccination can partially restore its effectiveness. Additionally, the Omicron variant exhibits distinct cell entry pathways and phenotypes, which may contribute to its rapid global spread and altered pathogenicity.

NATURE MICROBIOLOGY (2022)

Article Multidisciplinary Sciences

Imprinted antibody responses against SARS-CoV-2 Omicron sublineages

Young-Jun Park et al.

Summary: SARS-CoV-2 Omicron sublineages have spike mutations that allow them to evade antibodies from previous infection or vaccination. Hybrid immunity or booster shots can generate neutralizing antibodies against Omicron variants, and breakthrough infections lead to the production of neutralizing antibodies in the nasal mucosa. Antibodies derived from memory B cells or plasma cells of Omicron breakthrough cases show cross-reactivity with different receptor-binding domains, while primary Omicron infections elicit B cells with narrow specificity. A highly potent pan-variant-neutralizing antibody has been identified as a potential candidate for clinical development.

SCIENCE (2022)

Article Biochemistry & Molecular Biology

Cross-reactivity of eight SARS-CoV-2 variants rationally predicts immunogenicity clustering in sarbecoviruses

Qianqian Li et al.

Summary: A steep rise in Omicron reinfection cases indicates that this variant has enhanced immune evasion ability. Antisera from guinea pigs immunized with spike protein of SARS-CoV-2 variants of concern (VOCs) and variants of interest (VOIs) were cross-tested against pseudotyped variants to evaluate their antigenicity relationship. The study found that the neutralization activity against Omicron was significantly reduced when other VOCs or VOIs were used as immunogens. However, administering a Beta or Omicron booster as the 4th dose 3 months after the 3rd dose of any variant could elicit broad neutralizing antibodies against all current variants, including Omicron BA.1. Further analysis and quantification of immune escape from reported neutralizing antibodies provided explanations for the observed differential immunogenicity. An in silico algorithm predicted three distinct clades based on immune escape, which can be crucial for designing vaccines.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2022)

Article Multidisciplinary Sciences

The coding capacity of SARS-CoV-2

Yaara Finkel et al.

Summary: A high-resolution map of coding regions in the SARS-CoV-2 genome enables the identification of 23 unannotated open reading frames and quantification of the expression of canonical viral open reading frames.

NATURE (2021)

Article Microbiology

Complete Mapping of Mutations to the SARS-CoV-2 Spike Receptor-Binding Domain that Escape Antibody Recognition

Allison J. Greaney et al.

Summary: Antibodies targeting the SARS-CoV-2 spike receptor-binding domain (RBD) are key in neutralizing antibody responses, and a deep mutational scanning method was used to assess the impact of all amino-acid mutations in the RBD on antibody binding with 10 human monoclonal antibodies. The study identified the clustered escape mutations in different surfaces of the RBD that correspond to structurally defined antibody epitopes, showing that even antibodies targeting the same surface can have distinct escape mutations.

CELL HOST & MICROBE (2021)

Review Biochemistry & Molecular Biology

Structural and functional insights into the spike protein mutations of emerging SARS-CoV-2 variants

Deepali Gupta et al.

Summary: Since the emergence of COVID-19, the SARS-CoV-2 virus has been rapidly mutating, leading to various variants that affect transmission and virulence rates. Global infections and deaths have increased significantly, as the viral Spike protein interacts with host cells by binding to the hACE2 receptor.

CELLULAR AND MOLECULAR LIFE SCIENCES (2021)

Article Multidisciplinary Sciences

Loss of furin cleavage site attenuates SARS-CoV-2 pathogenesis

Bryan A. Johnson et al.

Summary: The genetic mutation in SARS-CoV-2 resulted in better fitness in some cells but lower replication capacity in human respiratory cell lines. Despite reducing disease symptoms, the Delta PRRA mutant provided protection against rechallenge with the wildtype SARS-CoV-2.

NATURE (2021)

Article Multidisciplinary Sciences

Prospective mapping of viral mutations that escape antibodies used to treat COVID-19

Tyler N. Starr et al.

Summary: Research has found that mutations in the receptor binding domain (RBD) of SARS-CoV-2 may potentially escape the action of the REGN-COV2 cocktail, providing important information for interpreting mutations observed during viral surveillance.

SCIENCE (2021)

Article Microbiology

The SARS-CoV-2 RNA-protein interactome in infected human cells

Nora Schmidt et al.

Summary: Characterizing the interactions between SARS-CoV-2 viral RNAs and host cell proteins during infection can enhance our understanding of viral RNA functions and the host innate immune response. Identification of specific host proteins that restrict viral replication and exploring defense strategies will aid in the development of targeted therapeutics against SARS-CoV-2.

NATURE MICROBIOLOGY (2021)

Article Multidisciplinary Sciences

Conformational dynamics of SARS-CoV-2 trimeric spike glycoprotein in complex with receptor ACE2 revealed by cryo-EM

Cong Xu et al.

Summary: The recent global health emergency caused by SARS-CoV-2 outbreak is mediated by the interaction between the SARS-CoV-2 trimeric spike glycoprotein and the human ACE2 receptor. The SARS-CoV-2 S trimer is more sensitive to ACE2 receptor compared to SARS-CoV S trimer, potentially contributing to its superior infectivity. Research findings depict the mechanism of ACE2-induced conformational transitions in S trimer structure, aiding in the development of anti-SARS-CoV-2 vaccines and therapeutics.

SCIENCE ADVANCES (2021)

Article Biochemistry & Molecular Biology

Rapid characterization of spike variants via mammalian cell surface display

Kamyab Javanmardi et al.

Summary: The Spike Display platform characterized 200 variant SARS-CoV-2 spikes, revealing a public epitope in the N-terminal domain loops that is recognized by most NTD-binding nAbs. Mutations in NTDs of variants like B.1.1.7, B.1.351, B.1.1.28, B.1.427/B.1.429, and B.1.617.2 impact spike expression and escape most NTD-targeting nAbs. Certain variants like B.1.351 and B.1.1.28 completely evade binding by a potent ACE2 mimic.

MOLECULAR CELL (2021)

Article Multidisciplinary Sciences

Functional and genetic analysis of viral receptor ACE2 orthologs reveals a broad potential host range of SARS-CoV-2

Yinghui Liu et al.

Summary: Epidemiological studies have shown that bats are the natural reservoir of SARS-CoV-2, but the host range and intermediate hosts for transmission are unknown. This study characterized the ability of ACE2 from various species to support viral entry, suggesting a potentially broad host tropism of SARS-CoV-2. Analysis of ACE2 orthologs revealed that New World monkey ACE2 could not support viral entry, with genetic determinants restricting this interaction.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2021)

Review Biochemistry & Molecular Biology

The origins of SARS-CoV-2: A critical review

Edward C. Holmes et al.

Summary: This article critically reviews the current scientific evidence to help clarify the origin of SARS-CoV-2. Recent debate has centered around two competing ideas: a laboratory escape scenario and zoonotic emergence.
Review Biochemistry & Molecular Biology

The next phase of SARS-CoV-2 surveillance: real-time molecular epidemiology

Bas B. Oude Munnink et al.

Summary: This review summarizes the current knowledge on key viral mutations and variants, emphasizing the need for a systematic approach to link global genomic surveillance with timely assessment of the phenotypic characteristics of novel variants in preparation for the next phase of the pandemic.

NATURE MEDICINE (2021)

Article Multidisciplinary Sciences

Defining variant-resistant epitopes targeted by SARS-CoV-2 antibodies: A global consortium study

Kathryn M. Hastie et al.

Summary: Antibody-based therapeutics and vaccines are crucial in combating COVID-19, especially with mutations and transmission of SARS-CoV-2. An international consortium identified multiple RBD-directed antibody communities, providing a framework for selecting treatment cocktails.

SCIENCE (2021)

Article Multidisciplinary Sciences

Effect of natural mutations of SARS-CoV-2 on spike structure, conformation, and antigenicity

Sophie M-C Gobeil et al.

Summary: SARS-CoV-2 variants with multiple spike mutations have increased transmission and resistance to antibodies. Research showed that these variants have enhanced receptor binding and a preference for receptor binding domain up states. Different variants exhibit different mechanisms for resistance to neutralizing antibodies, which helps explain their transmission and resistance.

SCIENCE (2021)

Article Multidisciplinary Sciences

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

Allison J. Greaney et al.

Summary: The study found that although the human immune system can produce antibodies that target diverse RBD epitopes, in practice, the polyclonal response to infection tends to be skewed towards a single class of antibodies targeting an epitope that is already undergoing rapid evolution.

NATURE COMMUNICATIONS (2021)

Article Cell Biology

One-shot identification of SARS-CoV-2 S RBD escape mutants using yeast screening

Irene M. Francino-Urdaniz et al.

Summary: This study reveals the presence of escape mutants for five nAbs targeting the S receptor binding site, predominantly located on the periphery of the ACE2 recognition site. The research team provides libraries, methods, and software as an openly available community resource to expedite the development of new therapeutic strategies against SARS-CoV-2.

CELL REPORTS (2021)

Article Biology

Effects of common mutations in the SARS-CoV-2 Spike RBD and its ligand, the human ACE2 receptor on binding affinity and kinetics

Michael Barton et al.

Summary: The study analyzed the effects of mutations in the Spike protein of SARS-CoV-2 on its interaction with ACE2, finding that most mutations increased affinity with ACE2. Two ACE2 mutations were also found to enhance binding with the Spike protein.

ELIFE (2021)

Article Microbiology

SARS-CoV-2 variant prediction and antiviral drug design are enabled by RBD in vitro evolution

Jiri Zahradnik et al.

Summary: In vitro evolution of the SARS-CoV-2 spike protein receptor-binding domain successfully generated a high-affinity variant effective in inhibiting virus infection. Mutations present in more transmissible viruses were preferentially selected, and increased affinity to ACE2 was positively correlated with the incidence of RBD mutations in the population. The study also identified mutations with potential higher infectivity, and the high-affinity RBD variant showed efficacy in inhibiting infection in vitro and reducing clinical disease in a hamster model of SARS-CoV-2 challenge.

NATURE MICROBIOLOGY (2021)

Review Microbiology

Cellular host factors for SARS-CoV-2 infection

Jim Baggen et al.

Summary: This review summarizes proviral host factors required for SARS-CoV-2 infection, important cellular processes in SARS-CoV-2 replication, and host factors that could be targeted for antiviral therapies for COVID-19.

NATURE MICROBIOLOGY (2021)

Review Biochemistry & Molecular Biology

The glycosylation in SARS-CoV-2 and its receptor ACE2

Yanqiu Gong et al.

Summary: This article reviews the detection, substrates, biological functions of glycosylation in SARS-CoV-2 proteins, as well as the human receptor ACE2. It also summarizes approved and ongoing SARS-CoV-2 therapeutics associated with glycosylation. This review not only helps broaden the understanding of viral glycobiology, but also provides key clues for the development of new preventive and therapeutic methodologies against SARS-CoV-2 and its variants.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2021)

Letter Infectious Diseases

An interactive web-based dashboard to track COVID-19 in real time

Ensheng Dong et al.

LANCET INFECTIOUS DISEASES (2020)

Article Multidisciplinary Sciences

Structural basis for the recognition of SARS-CoV-2 by full-length human ACE2

Renhong Yan et al.

SCIENCE (2020)

Article Multidisciplinary Sciences

Cryo-EM structure of the 2019-nCoV spike in the prefusion conformation

Daniel Wrapp et al.

SCIENCE (2020)

Article Biochemistry & Molecular Biology

Structural and Functional Basis of SARS-CoV-2 Entry by Using Human ACE2

Qihui Wang et al.

Article Biochemistry & Molecular Biology

The Architecture of SARS-CoV-2 Transcriptome

Dongwan Kim et al.

Article Biochemistry & Molecular Biology

Structure, Function, and Antigenicity of the SARS-CoV-2 Spike Glycoprotein

Alexandra C. Walls et al.

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)

Article Multidisciplinary Sciences

Site-specific glycan analysis of the SARS-CoV-2 spike

Yasunori Watanabe et al.

SCIENCE (2020)

Article Multidisciplinary Sciences

Human neutralizing antibodies elicited by SARS-CoV-2 infection

Bin Ju et al.

NATURE (2020)

Article Multidisciplinary Sciences

Structural basis of receptor recognition by SARS-CoV-2

Jian Shang et al.

NATURE (2020)

Article Biochemistry & Molecular Biology

The Impact of Mutations in SARS-CoV-2 Spike on Viral Infectivity and Antigenicity

Qianqian Li et al.

Article Biochemistry & Molecular Biology

A Thermostable mRNA Vaccine against COVID-19

Na-Na Zhang et al.

Article Microbiology

A dynamic nomenclature proposal for SARS-CoV-2 lineages to assist genomic epidemiology

Andrew Rambaut et al.

NATURE MICROBIOLOGY (2020)

Article Biochemistry & Molecular Biology

The protein expression profile of ACE2 in human tissues

Feria Hikmet et al.

MOLECULAR SYSTEMS BIOLOGY (2020)

Article Biochemistry & Molecular Biology

Molecular Architecture of the SARS-CoV-2 Virus

Hangping Yao et al.

Article Multidisciplinary Sciences

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

Ching-Lin Hsieh et al.

SCIENCE (2020)

Article Multidisciplinary Sciences

Studies in humanized mice and convalescent humans yield a SARS-CoV-2 antibody cocktail

Johanna Hansen et al.

SCIENCE (2020)

Article Multidisciplinary Sciences

Distinct conformational states of SARS-CoV-2 spike protein

Yongfei Cai et al.

SCIENCE (2020)

Article Multidisciplinary Sciences

Structures and distributions of SARS-CoV-2 spike proteins on intact virions

Zunlong Ke et al.

NATURE (2020)

Article Biochemical Research Methods

Quantification of SARS-CoV-2 neutralizing antibody by a pseudotyped virus-based assay

Jianhui Nie et al.

NATURE PROTOCOLS (2020)

Article Multidisciplinary Sciences

Broad host range of SARS-CoV-2 predicted by comparative and structural analysis of ACE2 in vertebrates

Joana Damas et al.

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

Article Immunology

Establishment and validation of a pseudovirus neutralization assay for SARS-CoV-2

Jianhui Nie et al.

EMERGING MICROBES & INFECTIONS (2020)