4.8 Article

Development of optimized drug-like small molecule inhibitors of the SARS-CoV-2 3CL protease for treatment of COVID-19

相关参考文献

注意:仅列出部分参考文献,下载原文获取全部文献信息。
Review Microbiology

Characteristics of SARS-CoV-2 and COVID-19

Ben Hu et al.

Summary: This review summarizes the research progress on SARS-CoV-2 and COVID-19, including virology characteristics, pathogenesis, and recent advances in treatment methods. Furthermore, it discusses in detail the potential wildlife hosts and zoonotic origin of this emerging virus.

NATURE REVIEWS MICROBIOLOGY (2021)

Article Chemistry, Medicinal

Improved SARS-CoV-2 Mpro inhibitors based on feline antiviral drug GC376: Structural enhancements, increased solubility, and micellar studies

Wayne Vuong et al.

Summary: The study demonstrates that GC376 and its derivatives are effective inhibitors of Mpro in SARS-CoV-2, with improved affinity and therapeutic index. Crystallographic analysis reveals an alternative binding pocket in M-pro and the mechanism of alternative binding induced by polar groups or a nearby methyl. Additionally, new findings on solubility and colloidal formation in aqueous media are reported, along with the use of choline to increase solubility.

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY (2021)

Article Pharmacology & Pharmacy

Dual inhibition of SARS-CoV-2 and human rhinovirus with protease inhibitors in clinical development

Cheng Liu et al.

Summary: The study evaluated SARS-CoV-2 3CLpro inhibitors using a novel enzymatic assay combining SAMDI-MS and rhinovirus HRV3C protease, showing high substrate specificity for each enzyme. The inhibitors were classified into three categories based on their potency against 3CLpro and HRV3C, guiding the design of virus-specific or broad-spectrum cysteine protease inhibitors against coronaviruses and rhinoviruses.

ANTIVIRAL RESEARCH (2021)

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)

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)

Article Multidisciplinary Sciences

SARS-CoV-2 M-pro inhibitors with antiviral activity in a transgenic mouse model

Jingxin Qiao et al.

Summary: The study designed and synthesized 32 new M-pro inhibitors containing bicycloproline, which showed inhibitory effects on SARS-CoV-2. Compounds MI-09 and MI-30 exhibited excellent antiviral activity in cell-based assays and significantly reduced lung viral loads and lung lesions in a transgenic mouse model of SARS-CoV-2 infection. Both also displayed good pharmacokinetic properties and safety in rats.

SCIENCE (2021)

Article Chemistry, Medicinal

Challenges for Targeting SARS-CoV-2 Proteases as a Therapeutic Strategy for COVID-19

Kas Steuten et al.

Summary: Two proteases produced by the SARS-CoV-2 virus play essential roles in viral replication, but inhibitors may also affect host cells; careful assessment of the selectivity of protease inhibitors is needed during drug development to avoid unnecessary interference with redundant pathways for viral entry.

ACS INFECTIOUS DISEASES (2021)

Article Multidisciplinary Sciences

Preclinical characterization of an intravenous coronavirus 3CL protease inhibitor for the potential treatment of COVID19

Britton Boras et al.

Summary: Researchers found that PF-07304814 exhibits broad-spectrum activity in inhibiting SARS-CoV and SARS-CoV-2, supported by its ADME and safety profile for clinical development. The 3CL protease, crucial in various coronaviruses, is effectively inhibited by PF-00835231 as a single agent, and shows even better results in combination with remdesivir.

NATURE COMMUNICATIONS (2021)

Article Biochemistry & Molecular Biology

ALG-097111, a potent and selective SARS-CoV-2 3-chymotrypsin-like cysteine protease inhibitor exhibits in vivo efficacy in a Syrian Hamster model

Koen Vandyck et al.

Summary: There is an urgent need for antivirals targeting SARS-CoV-2 virus. SARS-CoV-2 main protease (3CLpro) is a promising target for antiviral therapy, but selectivity issues of inhibitors need to be addressed. ALG-097111 demonstrated potent inhibition of SARS-CoV-2 3CLpro in vivo, providing evidence for its potential as a therapeutic target.

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS (2021)

Article Virology

Inhibitors of Coronavirus 3CL Proteases Protect Cells from Protease-Mediated Cytotoxicity

Samuel J. Resnick et al.

Summary: The study developed a simplified cell-based assay for identifying chemical inhibitors of a wide range of coronavirus 3CL proteases, which can be widely used in laboratories. The assay, without the need for live virus, is suitable for high-throughput screening and has identified broad-spectrum inhibitors.

JOURNAL OF VIROLOGY (2021)

Article Multidisciplinary Sciences

X-ray screening identifies active site and allosteric inhibitors of SARS-CoV-2 main protease

Sebastian Guenther et al.

Summary: The study identified 37 compounds that bind to the SARS-CoV-2 main protease through a high-throughput x-ray crystallographic screen of two repurposing drug libraries. Among these compounds, one peptidomimetic and six nonpeptidic compounds showed antiviral activity in cell-based viral reduction assays at nontoxic concentrations. The identification of two allosteric binding sites presents potential targets for drug development against SARS-CoV-2.

SCIENCE (2021)

Article Multidisciplinary Sciences

Lead compounds for the development of SARS-CoV-2 3CL protease inhibitors

Sho Iketani et al.

Summary: The study identifies three structurally diverse compounds as inhibitors of the SARS-CoV-2 3CL protease and provides insights for designing improved inhibitors.

NATURE COMMUNICATIONS (2021)

Article Multidisciplinary Sciences

Efficacy of GC-376 against SARS-CoV-2 virus infection in the K18 hACE2 transgenic mouse model

C. Joaquin Caceres et al.

Summary: GC-376 treatment showed slight improvement in survival in mice challenged with a high virus dose, but overall clinical symptoms and survival were not significantly improved. However, GC-376 treatment led to milder tissue lesions, reduced viral loads, and decreased inflammation in mice challenged with a low virus dose.

SCIENTIFIC REPORTS (2021)

Article Multidisciplinary Sciences

Identification of pyrogallol as a warhead in design of covalent inhibitors for the SARS-CoV-2 3CL protease

Haixia Su et al.

Summary: The naturally occurring flavonoid myricetin is identified as a non-peptidomimetic and covalent inhibitor of SARS-CoV-2 3CL protease. Crystal structures reveal the pyrogallol group modifies the catalytic cysteine through covalent binding. This study provides insights into the mechanism of action of pyrogallol-containing natural products and offers a template for designing non-peptidomimetic covalent inhibitors against 3CL proteases.

NATURE COMMUNICATIONS (2021)

Article Biochemistry & Molecular Biology

Cathepsin L plays a key role in SARS-CoV-2 infection in humans and humanized mice and is a promising target for new drug development

Miao-Miao Zhao et al.

Summary: CTSL plays a crucial role in COVID-19 patients, with its levels positively correlated with disease severity. Research showed that CTSL promotes SARS-CoV-2 virus entry into cells, and the CTSL inhibitor amantadine can inhibit this process, providing a direction for the development of new anti-COVID-19 drugs.

SIGNAL TRANSDUCTION AND TARGETED THERAPY (2021)

Article Multidisciplinary Sciences

A new coronavirus associated with human respiratory disease in China

Fan Wu et al.

NATURE (2020)

Article Multidisciplinary Sciences

A pneumonia outbreak associated with a new coronavirus of probable bat origin

Peng Zhou et al.

NATURE (2020)

Article Microbiology

An Infectious cDNA Clone of SARS-CoV-2

Xuping Xie et al.

CELL HOST & MICROBE (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

DNA vaccine protection against SARS-CoV-2 in rhesus macaques

Jingyou Yu et al.

SCIENCE (2020)

Article Chemistry, Multidisciplinary

2-Sulfonylpyridines as Tunable, Cysteine-Reactive Electrophiles

Claudio Zambaldo et al.

JOURNAL OF THE AMERICAN CHEMICAL SOCIETY (2020)

Article Multidisciplinary Sciences

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

Zhenming Jin et al.

NATURE (2020)

Article Biochemistry & Molecular Biology

Structural basis for the inhibition of SARS-CoV-2 main protease by antineoplastic drug carmofur

Zhenming Jin et al.

NATURE STRUCTURAL & MOLECULAR BIOLOGY (2020)

Review Pharmacology & Pharmacy

Cathepsin L-selective inhibitors: A potentially promising treatment for COVID-19 patients

Tianxiao Liu et al.

PHARMACOLOGY & THERAPEUTICS (2020)

Editorial Material Medicine, General & Internal

The Covid-19 Vaccine-Development Multiverse

Penny M. Heaton

NEW ENGLAND JOURNAL OF MEDICINE (2020)

Article Medicine, General & Internal

An mRNA Vaccine against SARS-CoV-2-Preliminary Report

L. A. Jackson et al.

NEW ENGLAND JOURNAL OF MEDICINE (2020)

Article Multidisciplinary Sciences

Feline coronavirus drug inhibits the main protease of SARS-CoV-2 and blocks virus replication

Wayne Vuong et al.

NATURE COMMUNICATIONS (2020)

Review Immunology

Cathepsin L in COVID-19: From Pharmacological Evidences to Genetics

Caio P. Gomes et al.

FRONTIERS IN CELLULAR AND INFECTION MICROBIOLOGY (2020)

Article Chemistry, Medicinal

Identification of SARS-CoV-2 3CL Protease Inhibitors by a Quantitative High-Throughput Screening

Wei Zhu et al.

ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE (2020)

Article Veterinary Sciences

Efficacy of a 3C-like protease inhibitor in treating various forms of acquired feline infectious peritonitis

Niels C. Pedersen et al.

JOURNAL OF FELINE MEDICINE AND SURGERY (2018)

Article Biochemistry & Molecular Biology

CellProfiler 3.0: Next-generation image processing for biology

Claire McQuin et al.

PLOS BIOLOGY (2018)

Article Biochemical Research Methods

A Perspective on the Kinetics of Covalent and Irreversible Inhibition

John M. Strelow

SLAS DISCOVERY (2017)

Article Pharmacology & Pharmacy

Hepatitis C virus NS3/4a protease inhibitors

John A. McCauley et al.

CURRENT OPINION IN PHARMACOLOGY (2016)

Article Chemistry, Medicinal

Recent Progress in the Development of HIV-1 Protease Inhibitors for the Treatment of HIV/AIDS

Arun K. Ghosh et al.

JOURNAL OF MEDICINAL CHEMISTRY (2016)

Article Biochemical Research Methods

Molecular replacement with MOLREP

Alexei Vagin et al.

ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY (2010)

Article Biochemical Research Methods

Integration, scaling, space-group assignment and post-refinement

Wolfgang Kabsch

ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY (2010)

Article Biochemical Research Methods

Features and development of Coot

P. Emsley et al.

ACTA CRYSTALLOGRAPHICA SECTION D-BIOLOGICAL CRYSTALLOGRAPHY (2010)

Article Biochemical Research Methods

PHENIX: a comprehensive Python-based system for macromolecular structure solution

Paul D. Adams et al.

ACTA CRYSTALLOGRAPHICA SECTION D-STRUCTURAL BIOLOGY (2010)

Article Pharmacology & Pharmacy

Mechanism-based inactivation of human cytochrome P450 enzymes and the prediction of drug-drug interactions

R. Scott Obach et al.

DRUG METABOLISM AND DISPOSITION (2007)

Article Biochemistry & Molecular Biology

High-throughput screening identifies inhibitors of the SARS coronavirus main proteinase

JE Blanchard et al.

CHEMISTRY & BIOLOGY (2004)

Article Biochemical Research Methods

Improved statistical methods for hit selection in high-throughput screening

C Brideau et al.

JOURNAL OF BIOMOLECULAR SCREENING (2003)

Article Biochemistry & Molecular Biology

A deliberate approach to screening for initial crystallization conditions of biological macromolecules

JR Luft et al.

JOURNAL OF STRUCTURAL BIOLOGY (2003)

Review Pharmacology & Pharmacy

Metabolic stability for drug discovery and development - Pharmacokinetic and biochemical challenges

CM Masimirembwa et al.

CLINICAL PHARMACOKINETICS (2003)

Article Medicine, General & Internal

HIV viral suppression in the era of antiretroviral therapy

HK Thaker et al.

POSTGRADUATE MEDICAL JOURNAL (2003)

Review Biochemistry & Molecular Biology

Prediction of pharmacokinetic properties using experimental approaches during early drug discovery

PR Chaturvedi et al.

CURRENT OPINION IN CHEMICAL BIOLOGY (2001)