4.6 Article

Discovery of Highly Potent Fusion Inhibitors with Potential Pan-Coronavirus Activity That Effectively Inhibit Major COVID-19 Variants of Concern (VOCs) in Pseudovirus-Based Assays

Related references

Note: Only part of the references are listed.
Article Biochemical Research Methods

Rationally Designed ACE2-Derived Peptides Inhibit SARS-CoV-2

Ross C. Larue et al.

Summary: The study identified ACE2-derived peptides that can effectively inhibit Spike-mediated infection of SARS-CoV-2 and related coronaviruses. Some of these peptides demonstrated inhibition of infection in low millimolar range and were found to target an ACE2 motif crucial for SARS-CoV-2 inhibition. These findings suggest the potential for developing peptide-based inhibitors for the treatment of COVID-19.

BIOCONJUGATE CHEMISTRY (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)

Review Virology

Domains and Functions of Spike Protein in SARS-Cov-2 in the Context of Vaccine Design

Xuhua Xia

Summary: This article delves into the structure and function of the spike protein in SARS-CoV-2, aiming to enhance the mechanistic understanding of how it mediates cell entry and transmission, as well as discussing important issues related to vaccine development and the emergence of viral variants.

VIRUSES-BASEL (2021)

Review Microbiology

The variant gambit: COVID-19's next move

Jessica A. Plante et al.

Summary: Despite the development of vaccines, COVID-19 caused by SARS-CoV-2 continues to be a global concern due to the emergence of new variants, raising worries about increased spread and potential impacts on immunity.

CELL HOST & MICROBE (2021)

Article Chemistry, Physical

Kobophenol A Inhibits Binding of Host ACE2 Receptor with Spike RBD Domain of SARS-CoV-2, a Lead Compound for Blocking COVID-19

Suresh Gangadevi et al.

Summary: The study revealed that Kobophenol A, identified through virtual screening, could potentially serve as an inhibitor for COVID-19 by blocking the interaction between the virus and cells, inhibiting viral infection. Molecular dynamics simulations indicated strong affinity of Kobophenol A to the ACE2 receptor, making it a promising compound for antiviral therapy.

JOURNAL OF PHYSICAL CHEMISTRY LETTERS (2021)

Article Virology

SARS-CoV-2 and SARS-CoV Spike-Mediated Cell-Cell Fusion Differ in Their Requirements for Receptor Expression and Proteolytic Activation

Bojan F. Hoernich et al.

Summary: The SARS-CoV-2 infects cells through spike protein interaction with ACE2 and activation by proteases, showing a greater dependence on ACE2 expression and metalloproteases for cell-cell fusion compared to SARS-CoV. The inhibitor bromhexine has been reported to enhance cell fusion in the presence of TMPRSS2, cautioning against its high dosage use until further understanding of its effects on SARS-CoV-2 spike activation.

JOURNAL OF VIROLOGY (2021)

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)

Article Biochemistry & Molecular Biology

Neutralization of SARS-CoV-2 spike 69/70 deletion, E484K and N501Y variants by BNT162b2 vaccine-elicited sera

Xuping Xie et al.

Summary: The study found that human sera from recipients of the BNT162b2 vaccine can neutralize SARS-CoV-2 viruses containing key spike mutations from the newly emerged UK and SA variants.

NATURE MEDICINE (2021)

Article Multidisciplinary Sciences

Recurrent deletions in the SARS-CoV-2 spike glycoprotein drive antibody escape

Kevin R. McCarthy et al.

Summary: The translation above discusses zoonotic pandemics caused by animal viruses spilling over into highly susceptible human populations, specifically focusing on the evolution of coronaviruses in human hosts and the impact of recurrent deletions in the spike glycoprotein on antibody epitopes. These studies help understand the antigenic evolution and adaptive evolution of SARS-CoV-2.

SCIENCE (2021)

Article Multidisciplinary Sciences

Blockade of SARS-CoV-2 spike protein-mediated cell-cell fusion using COVID-19 convalescent plasma

Ling Wang et al.

Summary: High titers of IgG neutralizing antibodies in COVID-19 convalescent plasma can block virus entry and fusion mediated by SARS-CoV-2-S, suggesting its potential as a preventive and therapeutic agent against SARS-CoV-2 and other SARS-CoV infections.

SCIENTIFIC REPORTS (2021)

Review Pharmacology & Pharmacy

Gains from no real PAINS: Where 'Fair Trial Strategy' stands in the development of multi-target ligands

Jianbo Sun et al.

Summary: The development of compounds with selectivity for multiple targets is hindered by the presence of PAINS suspects, which can result in false positive data. Extensive offline experiments are necessary to distinguish between harmful and beneficial compounds after online filtering.

ACTA PHARMACEUTICA SINICA B (2021)

Editorial Material Pharmacology & Pharmacy

Evolution of assay interference concepts in drug discovery

Juergen Bajorath

EXPERT OPINION ON DRUG DISCOVERY (2021)

Article Chemistry, Medicinal

Toward an Understanding of Pan-Assay Interference Compounds and Promiscuity: A Structural Perspective on Binding Modes

Sarah Naomi Bolz et al.

Summary: PAINS are promiscuous compound classes that produce false positive hits in high-throughput screenings. The mechanisms of PAINS activity are poorly understood, but recent studies have shown that they can mediate noncovalent interactions. Different PAINS classes exhibit varying levels of binding mode conservation, with some classes able to bind with high affinity despite variable binding modes.

JOURNAL OF CHEMICAL INFORMATION AND MODELING (2021)

Review Virology

Neutralising antibody escape of SARS-CoV-2 spike protein: Risk assessment for antibody-based Covid-19 therapeutics and vaccines

Daniele Focosi et al.

Summary: The Spike protein serves as the target for antibody-based therapeutics and vaccines, but mutations in Spike could impact their efficacy. Monitoring mutations is crucial for adjusting the therapeutics inventory. Different clades exhibit varying mutation combinations, with a focus on the UK, South African, and Brazilian variants.

REVIEWS IN MEDICAL VIROLOGY (2021)

Editorial Material Critical Care Medicine

SARS-CoV-2 evolution and vaccines: cause for concern?

Thomas C. Williams et al.

LANCET RESPIRATORY MEDICINE (2021)

Article Biochemistry & Molecular Biology

TMPRSS2 expression dictates the entry route used by SARS-CoV-2 to infect host cells

Jana Koch et al.

Summary: SARS-CoV-2 infects cells through two mutually exclusive pathways depending on the presence of TMPRSS2 protease. In the presence of TMPRSS2, the virus swiftly enters through the plasma membrane in a pH-independent manner; while in the absence of TMPRSS2, the virus is endocytosed and enters the cytosol post-infection.

EMBO JOURNAL (2021)

Editorial Material Medicine, General & Internal

Variants of SARS-CoV-2

Adam S. Lauring et al.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2021)

Letter Infectious Diseases

Rate and risk factors for breakthrough SARS-CoV-2 infection after vaccination

Adeel A. Butt et al.

JOURNAL OF INFECTION (2021)

Article Multidisciplinary Sciences

Reduced sensitivity of SARS-CoV-2 variant Delta to antibody neutralization

Delphine Planas et al.

Summary: The SARS-CoV-2 B.1.617 Delta variant, first identified in India in 2020, has become dominant in some regions and is spreading to many countries. This variant shows resistance to certain monoclonal antibodies and antibodies in convalescent sera, as well as reduced neutralization by some COVID-19 vaccines. Administration of two doses of the vaccine is needed for a neutralizing response against the Delta variant.

NATURE (2021)

Article Multidisciplinary Sciences

How the Delta variant achieves its ultrafast spread

Sara Reardon

NATURE (2021)

News Item Medicine, General & Internal

Delta variant: What is happening with transmission, hospital admissions, and restrictions?

Elisabeth Mahase

BMJ-BRITISH MEDICAL JOURNAL (2021)

Article Cell Biology

ACE2-Independent Interaction of SARS-CoV-2 Spike Protein with Human Epithelial Cells Is Inhibited by Unfractionated Heparin

Lynda J. Partridge et al.

Summary: The spike protein of SARS-CoV-2 binds primarily to ACE2 on target cells but may also involve other receptors. Heparin and glycosaminoglycans such as heparan sulfate and dermatan sulfate can inhibit the binding of spike protein to cells, indicating potential interactions with host cells beyond ACE2.

CELLS (2021)

Article Medicine, General & Internal

Severe SARS-CoV-2 Breakthrough Reinfection With Delta Variant After Recovery From Breakthrough Infection by Alpha Variant in a Fully Vaccinated Health Worker

Jayanthi Shastri et al.

Summary: The study found that despite post-vaccination immunity and immunity acquired through past infection, breakthrough infections caused by Variants of Concern can still occur in COVID-19 cases. A patient in the study experienced breakthrough infections with the Alpha variant and the Delta variant, the latter resulting in severe illness even after boosting. The source of infection was established through clinical data and genetic sequencing.

FRONTIERS IN MEDICINE (2021)

Article Immunology

Pan-coronavirus fusion inhibitors possess potent inhibitory activity against HIV-1, HIV-2, and simian immunodeficiency virus

Danwei Yu et al.

Summary: Research on the mechanism of action of lipopeptide inhibitors such as EK1V1 and IPB02 against HIV-1 and other viruses revealed that their target is the HR1 region of HIV-1 gp41, showing different activities against HIV-1 resistant mutants. This serendipitous discovery provides critical information for the development of broad-spectrum antivirals.

EMERGING MICROBES & INFECTIONS (2021)

Review Biochemistry & Molecular Biology

Nuisance compounds in cellular assays

Jayme L. Dahlin et al.

Summary: Nuisance compounds, which can waste resources and erode scientific trust, are a major obstacle in realizing the full potential of chemical biology. Understanding and addressing these compounds in complex cell-based assays is essential for efficient drug discovery and research.

CELL CHEMICAL BIOLOGY (2021)

Review Pharmacology & Pharmacy

Recent developments in pharmaceutical salts: FDA approvals from 2015 to 2019

Sonali S. Bharate

Summary: Drugs with poor aqueous solubility can have low and unpredictable oral bioavailability, so it is important to find strategies to enhance solubility. Around half of the new molecular entities approved by the US FDA are pharmaceutical salts, which have been steadily growing since 1939. This review provides updates on 61 pharmaceutical salts approved by the FDA between 2015 and 2019, detailing their chemical structures and therapeutic indications.

DRUG DISCOVERY TODAY (2021)

Letter Immunology

Fusion mechanism of 2019-nCoV and fusion inhibitors targeting HR1 domain in spike protein

Shuai Xia et al.

CELLULAR & MOLECULAR IMMUNOLOGY (2020)

Editorial Material Medicine, General & Internal

The Novel Coronavirus Originating in Wuhan, China Challenges for Global Health Governance

Alexandra L. Phelan et al.

JAMA-JOURNAL OF THE AMERICAN MEDICAL ASSOCIATION (2020)

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

Immunogenicity of a DNA vaccine candidate for COVID-19

Trevor R. F. Smith et al.

NATURE COMMUNICATIONS (2020)

Review Pharmacology & Pharmacy

Coronavirus membrane fusion mechanism offers a potential target for antiviral development

Tiffany Tang et al.

ANTIVIRAL RESEARCH (2020)

Article Biochemistry & Molecular Biology

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

Qianqian Li et al.

Article Immunology

Measuring SARS-CoV-2 neutralizing antibody activity using pseudotyped and chimeric viruses

Fabian Schmidt et al.

JOURNAL OF EXPERIMENTAL MEDICINE (2020)

Article Biochemistry & Molecular Biology

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

Wei Li et al.

Article Multidisciplinary Sciences

De novo design of picomolar SARS-CoV-2 miniprotein inhibitors

Longxing Cao et al.

SCIENCE (2020)

Article Multidisciplinary Sciences

Molecular interaction and inhibition of SARS-CoV-2 binding to the ACE2 receptor

Jinsung Yang et al.

NATURE COMMUNICATIONS (2020)

Article Chemistry, Physical

Computational Design of 25-mer Peptide Binders of SARS-CoV-2

Thassanai Sitthiyotha et al.

JOURNAL OF PHYSICAL CHEMISTRY B (2020)

Article Pharmacology & Pharmacy

Potential Simultaneous Inhibitors of Angiotensin-Converting Enzyme 2 and Transmembrane Protease, Serine 2

Ching-Yuan Wu et al.

FRONTIERS IN PHARMACOLOGY (2020)

Article Multidisciplinary Sciences

De novo design of potent and resilient hACE2 decoys to neutralize SARS-CoV-2

Thomas W. Linsky et al.

SCIENCE (2020)

Article Immunology

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

Jianhui Nie et al.

EMERGING MICROBES & INFECTIONS (2020)

Article Biochemistry & Molecular Biology

Mutations in the SARS-CoV-2 spike RBD are responsible for stronger ACE2 binding and poor anti-SARS-CoV mAbs cross-neutralization

Masaud Shah et al.

COMPUTATIONAL AND STRUCTURAL BIOTECHNOLOGY JOURNAL (2020)

Review Chemistry, Multidisciplinary

Computational advances in combating colloidal aggregation in drug discovery

Daniel Reker et al.

NATURE CHEMISTRY (2019)

Editorial Material Health Care Sciences & Services

Vaccine hesitancy: Not a new phenomenon, but a new threat

Mary Koslap-Petraco

JOURNAL OF THE AMERICAN ASSOCIATION OF NURSE PRACTITIONERS (2019)

Review Biochemistry & Molecular Biology

Salts of Therapeutic Agents: Chemical, Physicochemical, and Biological Considerations

Deepak Gupta et al.

MOLECULES (2018)

Article Immunology

Enterokinase Enhances Influenza A Virus Infection by Activating Trypsinogen in Human Cell Lines

Hideki Hayashi et al.

FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY (2018)

Editorial Material Chemistry, Medicinal

The Ecstasy and Agony of Assay Interference Compounds

Courtney Aldrich et al.

ACS MEDICINAL CHEMISTRY LETTERS (2017)

Review Virology

Structure, Function, and Evolution of Coronavirus Spike Proteins

Fang Li

ANNUAL REVIEW OF VIROLOGY, VOL 3 (2016)

Review Pharmacology & Pharmacy

Role of Cytochrome P450 2C8 in Drug Metabolism and Interactions

Janne T. Backman et al.

PHARMACOLOGICAL REVIEWS (2016)

Article Biotechnology & Applied Microbiology

An analysis of the attrition of drug candidates from four major pharmaceutical companies

Michael J. Waring et al.

NATURE REVIEWS DRUG DISCOVERY (2015)

Article Virology

Macropinocytosis Is the Entry Mechanism of Amphotropic Murine Leukemia Virus

Izabela Rasmussen et al.

JOURNAL OF VIROLOGY (2015)

Editorial Material Multidisciplinary Sciences

Chemical con artists foil drug discovery

Jonathan Baell et al.

NATURE (2014)

Article Multidisciplinary Sciences

Structure-based discovery of Middle East respiratory syndrome coronavirus fusion inhibitor

Lu Lu et al.

NATURE COMMUNICATIONS (2014)

Article Chemistry, Medicinal

Colloidal Aggregation Causes Inhibition of G Protein-Coupled Receptors

Maria F. Sassano et al.

JOURNAL OF MEDICINAL CHEMISTRY (2013)

Article Computer Science, Interdisciplinary Applications

PKSolver: An add-in program for pharmacokinetic and pharmacodynamic data analysis in Microsoft Excel

Yong Zhang et al.

COMPUTER METHODS AND PROGRAMS IN BIOMEDICINE (2010)

Review Virology

Virus Cell-to-Cell Transmission

Walther Mothes et al.

JOURNAL OF VIROLOGY (2010)

Article Biotechnology & Applied Microbiology

The effect of plasma protein binding on in vivo efficacy: misconceptions in drug discovery

Dennis A. Smith et al.

NATURE REVIEWS DRUG DISCOVERY (2010)

Article Chemistry, Medicinal

Characterization of chemical libraries for luciferase inhibitory activity

Douglas S. Auld et al.

JOURNAL OF MEDICINAL CHEMISTRY (2008)

Article Chemistry, Multidisciplinary

Stoichiometry and physical chemistry of promiscuous aggregate-based inhibitors

Kristin E. D. Coan et al.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2008)

Letter Surgery

Gains from the separation of conjoined twins

Jiaming Sun et al.

PLASTIC AND RECONSTRUCTIVE SURGERY (2008)

Article Biochemistry & Molecular Biology

Resveratrol inhibits firefly luciferase

Adel Bakhtiarova et al.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2006)

Article Chemistry, Medicinal

Interpreting steep dose-response curves in early inhibitor discovery

Brian K. Shoichet

JOURNAL OF MEDICINAL CHEMISTRY (2006)

Article Biochemical Research Methods

A detergent-based assay for the detection of promiscuous inhibitors

Brian Y. Feng et al.

NATURE PROTOCOLS (2006)

Article Chemistry, Medicinal

Identification and prediction of promiscuous aggregating inhibitors among known drugs

J Seidler et al.

JOURNAL OF MEDICINAL CHEMISTRY (2003)

Article Chemistry, Medicinal

A specific mechanism of nonspecific inhibition

SL McGovern et al.

JOURNAL OF MEDICINAL CHEMISTRY (2003)

Article Chemistry, Medicinal

Effect of detergent on promiscuous inhibitors

AJ Ryan et al.

JOURNAL OF MEDICINAL CHEMISTRY (2003)

Article Chemistry, Medicinal

A common mechanism underlying promiscuous inhibitors from virtual and high-throughput screening

SL McGovern et al.

JOURNAL OF MEDICINAL CHEMISTRY (2002)