☆ 4.6 Article

A Versatile Class of 1,4,4-Trisubstituted Piperidines Block Coronavirus Replication In Vitro

PHARMACEUTICALS (2022)

Related references

Note: Only part of the references are listed.

Article Multidisciplinary Sciences

Broadly neutralizing antibodies overcome SARS-CoV-2 Omicron antigenic shift

Elisabetta Cameroni et al.

Summary: The Omicron variant of SARS-CoV-2 has raised concerns due to its 37 amino acid substitutions in the spike protein, particularly in the receptor-binding domain (RBD), leading to increased binding affinity with human ACE2. Neutralizing activity against Omicron was greatly reduced in convalescent and vaccinated individuals compared to the ancestral virus, but this decrease was less significant after a third vaccine dose. Broadly neutralizing monoclonal antibodies recognizing conserved RBD epitopes may be crucial in combating the Omicron variant and future zoonotic transmissions.

NATURE (2022)

Add to Collection

Review Cell Biology

Structures and functions of coronavirus replication-transcription complexes and their relevance for SARS-CoV-2 drug design

Brandon Malone et al.

Summary: The molecular basis and complexity of coronavirus RNA-synthesizing machinery is still not fully understood. Recent research has focused on deciphering and understanding the structures, functions, and interactions of the subunits involved in SARS-CoV-2 replication and transcription. Both viral and host factors play a crucial role in coordinating RNA translation, replication, and transcription, making them potential targets for antiviral therapy.

NATURE REVIEWS MOLECULAR CELL BIOLOGY (2022)

Add to Collection

Article Medicine, General & Internal

Molnupiravir for Oral Treatment of Covid-19 in Nonhospitalized Patients

A. Jayk Bernal et al.

Summary: This study found that early treatment with molnupiravir reduced the risk of hospitalization or death in at-risk, unvaccinated adults with Covid-19.

NEW ENGLAND JOURNAL OF MEDICINE (2022)

Add to Collection

Article Medicine, General & Internal

Oral Nirmatrelvir for High-Risk, Nonhospitalized Adults with Covid-19

Jennifer Hammond et al.

Summary: In high-risk, unvaccinated adults, treatment of Covid-19 with nirmatrelvir plus ritonavir can significantly reduce the risk of hospitalization and death, with good safety profile.

NEW ENGLAND JOURNAL OF MEDICINE (2022)

Add to Collection

Article Medicine, General & Internal

Early Remdesivir to Prevent Progression to Severe Covid-19 in Outpatients

R. L. Gottlieb et al.

Summary: In symptomatic, nonhospitalized high-risk Covid-19 patients, a 3-day course of remdesivir significantly reduced the risk of hospitalization or death compared to placebo, with acceptable safety profile.

NEW ENGLAND JOURNAL OF MEDICINE (2022)

Add to Collection

Article Biochemistry & Molecular Biology

PDBe-KB: collaboratively defining the biological context of structural data

Mihaly Varadi et al.

Summary: PDBe-KB is an open collaboration platform that aims to integrate functional and biophysical annotations from world-leading specialist data resources, serving the Protein Data Bank. By developing standardized data exchange formats and integrating functional annotations from partner resources, PDBe-KB aims to place macromolecular structure data in a biological context and provide valuable biological insights.

NUCLEIC ACIDS RESEARCH (2022)

Add to Collection

Article Chemistry, Multidisciplinary

Selective covalent targeting of SARS-CoV-2 main protease by enantiopure chlorofluoroacetamide

Daiki Yamane et al.

Summary: This study reports an irreversible inhibitor of SARS-CoV-2 M-pro with chlorofluoroacetamide (CFA) as a covalent modification agent. The (R,R)-18 isomer showed higher inhibitory activity against M-pro than other isomers. The findings highlight the influence of CFA chirality on the covalent modification of proteinous cysteines and provide a basis for improving the potency and selectivity of CFA-based covalent inhibitors.

CHEMICAL SCIENCE (2022)

Add to Collection

Article Multidisciplinary Sciences

A dual mechanism of action of AT-527 against SARS-CoV-2 polymerase

Ashleigh Shannon et al.

Summary: AT-527 is a promising candidate drug that targets the SARS-CoV-2 replication machinery by inhibiting the RNA-dependent RNA polymerase.

NATURE COMMUNICATIONS (2022)

Add to Collection

Article Biochemical Research Methods

Discovery of SARS-CoV-2 main protease covalent inhibitors from a DNA-encoded library selection

Rui Ge et al.

Summary: This study discovered two new series of molecules that irreversibly bind to the main protease of SARS-CoV-2 using a covalent DNA-encoded library screening platform. The results suggest that these molecules show reasonable selectivity for SARS-CoV-2 and demonstrate inhibitory effects against the protease enzymes of various coronavirus strains.

SLAS DISCOVERY (2022)

Add to Collection

Article Microbiology

Remdesivir and GS-441524 Retain Antiviral Activity against Delta, Omicron, and Other Emergent SARS-CoV-2 Variants

Jared Pitts et al.

Summary: Genetic variation of SARS-CoV-2 has led to the emergence and rapid spread of multiple variants, including Omicron. This study assessed the antiviral activity of Remdesivir and its parent nucleoside, GS-441524, against various SARS-CoV-2 variants. The results showed that Delta and Omicron variants remained susceptible to Remdesivir and GS-441524, while other variants exhibited varied susceptibility.

ANTIMICROBIAL AGENTS AND CHEMOTHERAPY (2022)

Add to Collection

Review Infectious Diseases

First-generation oral antivirals against SARS-CoV-2

Parham Sendi et al.

Summary: This article provides an overview of first-generation oral antiviral agents against SARS-CoV-2, including the authorized use of molnupiravir, nirmatrelvir, and ritonavir. These drugs have shown some efficacy in non-hospitalized, mild-to-moderate COVID-19 patients at high risk for clinical progression. However, their use in clinical practice requires attention to factors such as timing of administration, drug-drug interactions, embryo-fetal toxicity, and compliance with pill ingestion. Knowledge gaps remain regarding the efficacy of these agents in vaccinated, hospitalized, or immunosuppressed individuals.

CLINICAL MICROBIOLOGY AND INFECTION (2022)

Add to Collection

Article Biochemistry & Molecular Biology

Structural basis for the in vitro efficacy of nirmatrelvir against SARS-CoV-2 variants

Samantha E. Greasley et al.

Summary: The efficacy and potency of nirmatrelvir against different variants of SARS-CoV-2 were evaluated. The results showed that nirmatrelvir has similar potency against mutant M-pros, including Omicron, and can maintain high concentrations in cells to inhibit the replication of these variants.

JOURNAL OF BIOLOGICAL CHEMISTRY (2022)

Add to Collection

Article Chemistry, Medicinal

Potent Inhibition of SARS-CoV-2 nsp14 N7-Methyltransferase bySulfonamide-Based Bisubstrate Analogues

Rostom Ahmed-Belkacem et al.

Summary: This study focuses on the design and synthesis of inhibitors against SARS-CoV-2 enzymes involved in RNA capping, which are important for viral RNA stability, mRNA translation, and evasion of innate immunity. Seven compounds showed significant inhibitory activity, and the three most potent inhibitors stabilized the enzyme effectively.

JOURNAL OF MEDICINAL CHEMISTRY (2022)

Add to Collection

Article Multidisciplinary Sciences

Structural basis for replicase polyprotein cleavage and substrate specificity of main protease from SARS-CoV-2

Yao Zhao et al.

Summary: This study determines the high-resolution structures of SARS-CoV-2 M-Pro in different states, revealing the conformational changes that occur during substrate processing. The study also demonstrates the enzyme's specificity for certain sequences and provides a foundation for the development of new anti-SARS-CoV-2 drugs.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2022)

Add to Collection

Article Multidisciplinary Sciences

Covalent narlaprevir- and boceprevir-derived hybrid inhibitors of SARS-CoV-2 main protease

Daniel W. Kneller et al.

Summary: The study designed three covalent hybrid inhibitors that showed comparable antiviral activity to a known drug in vitro. The binding mechanism of these inhibitors to the viral main protease was also analyzed, providing important atomic and thermodynamic details.

NATURE COMMUNICATIONS (2022)

Add to Collection

Review Infectious Diseases

The efficacy and adverse effects of favipiravir on patients with COVID-19: A systematic review and meta-analysis of published clinical trials and observational studies

Dang The Hung et al.

Summary: Favipiravir has shown better outcomes for hospitalized COVID-19 patients, with improved viral clearance, defervescence, chest radiological improvement, hospital discharge rates, and shorter clinical improvement time. However, there are some adverse events associated with its use. No significant differences were observed in non-hospitalized patients.

INTERNATIONAL JOURNAL OF INFECTIOUS DISEASES (2022)

Add to Collection

Article Microbiology

Therapeutic efficacy of monoclonal antibodies and antivirals against SARS-CoV-2 Omicron BA.1 in Syrian hamsters

Ryuta Uraki et al.

Summary: This study assessed the efficacy of therapeutic monoclonal antibodies and antiviral drugs against the Omicron variant in Syrian hamsters. The results showed that only one therapeutic antibody could effectively inhibit the replication of the Omicron BA.1 variant, while antiviral drugs were able to reduce virus replication in the lungs.

NATURE MICROBIOLOGY (2022)

Add to Collection

Review Chemistry, Organic

Multicomponent synthesis of highly functionalized piperidines

Leili Shaker Ardakani et al.

Summary: Highly functionalized piperidines are versatile nitrogen-containing heterocycles with broad applications in fields such as medicinal chemistry and drug discovery research. The synthesis of this privileged scaffold from readily available materials remains a hot topic research for the synthetic chemistry community, with different strategies having been developed so far.

SYNTHETIC COMMUNICATIONS (2021)

Add to Collection

Article Chemistry, Medicinal

Perspectives on SARS-CoV-2 Main Protease Inhibitors

Kaifu Gao et al.

Summary: The M-pro enzyme is crucial for the replication of SARS-CoV-2 and is a prime therapeutic target. Despite the availability of numerous M-pro inhibitors, no approved medication for SARS-CoV-2 exists yet due to the lengthy drug development process. Additional research on the mechanisms of these inhibitors and their potential as future antiviral drugs is needed.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

Add to Collection

Article Biochemical Research Methods

A fluorescence-based high throughput-screening assay for the SARS-CoV RNA synthesis complex

Cecilia Eydoux et al.

Summary: The research on SARS-CoV has provided insights for combating SARS-CoV-2 by discovering a new method for identifying drug candidates. This has the potential to expedite the drug discovery process against SARS-CoV-2.

JOURNAL OF VIROLOGICAL METHODS (2021)

Add to Collection

Article Virology

A Comparative Analysis of SARS-CoV-2 Antivirals Characterizes 3CLpro Inhibitor PF-00835231 as a Potential New Treatment for COVID-19

Maren de Vries et al.

Summary: The study compares the efficacy of the potential antiviral drug PF-00835231 with other inhibitors on SARS-CoV-2 in vitro, showing that PF-00835231 has similar or higher potency. It targets the main protease of the virus, potentially providing a new treatment option for COVID-19.

JOURNAL OF VIROLOGY (2021)

Add to Collection

Article Multidisciplinary Sciences

An oral SARS-CoV-2 Mpro inhibitor clinical candidate for the treatment of COVID-19

Dafydd R. Owen et al.

Summary: PF-07321332, an orally bioavailable SARS-CoV-2 main protease inhibitor, has been discovered with in vitro pan-human coronavirus antiviral activity and excellent off-target selectivity and in vivo safety profiles. This new drug has shown promise in countering the threat of COVID-19 with its oral activity and safety in clinical trials.

SCIENCE (2021)

Add to Collection

Article Immunology

US201 Study: A Phase 2, Randomized Proof-of-Concept Trial of Favipiravir for the Treatment of COVID-19

Robert W. Finberg et al.

Summary: Favipiravir shows enhanced viral clearance in hospitalized adult patients with COVID-19 compared to standard of care, with a median time to viral clearance of 16.0 days in the favipiravir group and 30.0 days in the SOC group. Further studies are warranted to explore its potential in treating COVID-19.

OPEN FORUM INFECTIOUS DISEASES (2021)

Add to Collection

Article Chemistry, Medicinal

Betulonic Acid Derivatives Interfering with Human Coronavirus 229E Replication via the nsp15 Endoribonuclease

Annelies Stevaert et al.

Summary: This study identified a class of HCoV inhibitors targeting nsp15, with lead molecule 5h showing strong inhibitory effects on HCoV-229E replication. However, a mutant virus with nsp15 endoribonuclease active site mutation showed reduced sensitivity to 5h. The findings revealed a druggable pocket in the nsp15 hexamer with relevance for anti-coronavirus drug development.

JOURNAL OF MEDICINAL CHEMISTRY (2021)

Add to Collection

Article Microbiology

The SARS-CoV-2 and other human coronavirus spike proteins are fine-tuned towards temperature and proteases of the human airways

Manon Laporte et al.

Summary: The high transmissibility of SARS-CoV-2 is related to the virus's abundant replication in the upper airways, which differs from other highly pathogenic coronaviruses. The spike protein of SARS-CoV-2 exhibits intrinsic temperature preference, optimizing the virus for the human respiratory tract and enhancing its transmission. Additionally, certain proteases in the human airways play a key role in activating the spike protein for virus entry, further increasing SARS-CoV-2's ability to spread.

PLOS PATHOGENS (2021)

Add to Collection

Review Critical Care Medicine

What is the role of remdesivir in patients with COVID-19?

John H. Beigel

Summary: COVID-19, caused by SARS-CoV-2, is an unprecedented public health crisis. Remdesivir, an antiviral drug, is being evaluated for its efficacy in treating COVID-19 patients. Trials have shown mixed results, with some indicating benefits such as reduced hospital stays and lower need for mechanical ventilation. However, more data is needed to determine its overall effectiveness.

CURRENT OPINION IN CRITICAL CARE (2021)

Add to Collection

Article Chemistry, Medicinal

AutoDock Vina 1.2.0: New Docking Methods, Expanded Force Field, and Python Bindings

Jerome Eberhardt et al.

Summary: AutoDock Vina is a widely used open-source program for molecular docking with new features such as support for macrocycles and explicit water molecules. The latest version also includes support for AutoDock4.2 scoring function, simultaneous docking of multiple ligands, and a batch mode for docking a large number of ligands. Python bindings have been implemented to facilitate scripting and workflow development.

JOURNAL OF CHEMICAL INFORMATION AND MODELING (2021)

Add to Collection

Article Immunology

Report of the National Institutes of Health SARS-CoV-2 Antiviral Therapeutics Summit

Matthew D. Hall et al.

Summary: The NIH Virtual SARS-CoV-2 Antiviral Summit aimed to provide an overview of the status and challenges in developing antiviral therapeutics for COVID-19, with the goals of reviewing the current science, sharing insights, and identifying opportunities for collaboration.

JOURNAL OF INFECTIOUS DISEASES (2021)

Add to Collection

Review Pharmacology & Pharmacy

Piperidine nucleus in the field of drug discoveryY

Mennatallah Mahmoud Abdelshaheed et al.

Summary: Piperidine and its derivatives have versatile applications in medicine, serving as treatment options for various diseases. Recent studies have confirmed the significant role of the piperidine nucleus in drug discovery.

FUTURE JOURNAL OF PHARMACEUTICAL SCIENCES (2021)

Add to Collection

Review Microbiology

Coronavirus biology and replication: implications for SARS-CoV-2

Philip V'kovski et al.

Summary: This review discusses key aspects of coronavirus biology and their implications for SARS-CoV-2 infections, treatment, and prevention strategies. Understanding virus-host interactions at the molecular level is crucial for developing effective intervention strategies. Summarizing the discoveries of SARS-CoV-2 infection and comparing it with other coronaviruses will support future preparedness and combat strategies.

NATURE REVIEWS MICROBIOLOGY (2021)

Add to Collection

Article Biochemistry & Molecular Biology

SARS-CoV-2 Cell Entry Depends on ACE2 and TMPRSS2 and Is Blocked by a Clinically Proven Protease Inhibitor

Markus Hoffmann et al.

CELL (2020)

Add to Collection

Article Chemistry, Medicinal

N-benzyl 4,4-disubstituted piperidines as a potent class of influenza H1N1 virus inhibitors showing a novel mechanism of hemagglutinin fusion peptide interaction

Sonia de Castro et al.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2020)

Add to Collection

Article Multidisciplinary Sciences

Crystal structure of SARS-CoV-2 main protease provides a basis for design of improved α-ketoamide inhibitors

Linlin Zhang et al.

SCIENCE (2020)

Add to Collection

Article Multidisciplinary Sciences

Structure of Mpro from SARS-CoV-2 and discovery of its inhibitors

Zhenming Jin et al.

NATURE (2020)

Add to Collection

Article Medicine, General & Internal

Remdesivir for the Treatment of Covid-19-Final Report

John H. Beigel et al.

NEW ENGLAND JOURNAL OF MEDICINE (2020)

Add to Collection

Review Pharmacology & Pharmacy

Coronavirus membrane fusion mechanism offers a potential target for antiviral development

Tiffany Tang et al.

ANTIVIRAL RESEARCH (2020)

Add to Collection

Article Chemistry, Medicinal

Reprogramming of the Antibacterial Drug Vancomycin Results in Potent Antiviral Agents Devoid of Antibacterial Activity

Zsolt Szucs et al.

PHARMACEUTICALS (2020)

Add to Collection

Article Pharmacology & Pharmacy

Evaluation of SARS-CoV-2 3C-like protease inhibitors using self-assembled monolayer desorption ionization mass spectrometry

Zachary A. Gurard-Levin et al.

ANTIVIRAL RESEARCH (2020)

Add to Collection

Article Biochemistry & Molecular Biology

Prediction of ligand binding mode among multiple cross-docking poses by molecular dynamics simulations

Kai Liu et al.

JOURNAL OF COMPUTER-AIDED MOLECULAR DESIGN (2020)

Add to Collection

Article Chemistry, Medicinal

Discovery of Ketone-Based Covalent Inhibitors of Coronavirus 3CL Proteases for the Potential Therapeutic Treatment of COVID-19

Robert L. Hoffman et al.

JOURNAL OF MEDICINAL CHEMISTRY (2020)

Add to Collection

Article Multidisciplinary Sciences

Both Boceprevir and GC376 efficaciously inhibit SARS-CoV-2 by targeting its main protease

Lifeng Fu et al.

NATURE COMMUNICATIONS (2020)

Add to Collection

Article Multidisciplinary Sciences

Crystallographic and electrophilic fragment screening of the SARS-CoV-2 main protease

Alice Douangamath et al.

NATURE COMMUNICATIONS (2020)

Add to Collection

Review Chemistry, Multidisciplinary

Two decades of recent advances of Ugi reactions: synthetic and pharmaceutical applications

Manar Ahmed Fouad et al.

RSC ADVANCES (2020)

Add to Collection

Review Chemistry, Organic

Multicomponent Reactions for the Synthesis of Bioactive Compounds: A Review

Cedric S. Graebin et al.

CURRENT ORGANIC SYNTHESIS (2019)

Add to Collection

Article Virology

Antiviral activity of K22 against members of the order Nidovirales

Julie Christiane Francoise Rappe et al.

VIRUS RESEARCH (2018)

Add to Collection

Article Chemistry, Multidisciplinary

The Cambridge Structural Database

Colin R. Groom et al.

ACTA CRYSTALLOGRAPHICA SECTION B-STRUCTURAL SCIENCE CRYSTAL ENGINEERING AND MATERIALS (2016)

Add to Collection

Article Chemistry, Organic

Versatile Multicomponent Reaction Macrocycle Synthesis Using α-Isocyano-ω-carboxylic Acids

George P. Liao et al.

ORGANIC LETTERS (2015)

Add to Collection

Article Chemistry, Medicinal

Discovery and SAR studies of a novel class of cytotoxic 1,4-disubstituted piperidines via Ugi reaction

Sonia de Castro et al.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2014)

Add to Collection

Review Biochemistry & Molecular Biology

From SARS to MERS: crystallographic studies on coronaviral proteases enable antiviral drug design

Rolf Hilgenfeld

FEBS JOURNAL (2014)

Add to Collection

Article Multidisciplinary Sciences

One severe acute respiratory syndrome coronavirus protein complex integrates processive RNA polymerase and exonuclease activities

Lorenzo Subissi et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (2014)

Add to Collection

Article Microbiology

Correction: In Vitro Reconstitution of SARS-Coronavirus mRNA Cap Methylation

Mickaël Bouvet et al.

PLoS Pathogens (2014)

Add to Collection

Article Microbiology

Targeting Membrane-Bound Viral RNA Synthesis Reveals Potent Inhibition of Diverse Coronaviruses Including the Middle East Respiratory Syndrome Virus

Anna Lundin et al.

PLOS PATHOGENS (2014)

Add to Collection

Article Pharmacology & Pharmacy

Potent inhibition of feline coronaviruses with peptidyl compounds targeting coronavirus 3C-like protease

Yunjeong Kim et al.

ANTIVIRAL RESEARCH (2013)

Add to Collection

Article Immunology

Clinical Impact of Human Coronaviruses 229E and OC43 Infection in Diverse Adult Populations

Edward E. Walsh et al.

JOURNAL OF INFECTIOUS DISEASES (2013)

Add to Collection

Review Chemistry, Multidisciplinary

Chemistry and Biology Of Multicomponent Reactions

Alexander Domling et al.

CHEMICAL REVIEWS (2012)

Add to Collection

Review Medicine, General & Internal

Human Coronaviruses 229E and NL63: Close Yet Still So Far

Ronald Dijkman et al.

JOURNAL OF THE FORMOSAN MEDICAL ASSOCIATION (2009)

Add to Collection

Article Virology

Protease-Mediated Entry via the Endosome of Human Coronavirus 229E

Miyuki Kawase et al.

JOURNAL OF VIROLOGY (2009)

Add to Collection

Article Chemistry, Multidisciplinary

The implementation of a fast and accurate QM/MM potential method in Amber

Ross C. Walker et al.

JOURNAL OF COMPUTATIONAL CHEMISTRY (2008)

Add to Collection

Review Chemistry, Multidisciplinary

The Amber biomolecular simulation programs

DA Case et al.

JOURNAL OF COMPUTATIONAL CHEMISTRY (2005)

Add to Collection

Article Chemistry, Multidisciplinary

Development and testing of a general amber force field

JM Wang et al.

JOURNAL OF COMPUTATIONAL CHEMISTRY (2004)

Add to Collection

Article Multidisciplinary Sciences

Coronavirus main proteinase (3CLpro) structure:: Basis for design of anti-SARS drugs

K Anand et al.

SCIENCE (2003)

Add to Collection

Article Biochemistry & Molecular Biology

Structure of coronavirus main proteinase reveals combination of a chymotrypsin fold with an extra α-helical domain

K Anand et al.

EMBO JOURNAL (2002)

Add to Collection

Article Biochemistry & Molecular Biology

The Protein Data Bank

HM Berman et al.

NUCLEIC ACIDS RESEARCH (2000)

Add to Collection

© Peeref 2019-2024. All rights reserved.