4.7 Article

Evaluation of SARS-CoV-2 Main Protease Inhibitors Using a Novel Cell-Based Assay

Related references

Note: Only part of the references are listed.
Article Chemistry, Medicinal

MPI8 is Potent against SARS-CoV-2 by Inhibiting Dually and Selectively the SARS-CoV-2 Main Protease and the Host Cathepsin L**

Xinyu R. Ma et al.

Summary: Inhibitors targeting the SARS-CoV-2 main protease have been developed, with some showing high potency in inhibiting cathepsins B/K/L. Among them, MPI8 displays the best selectivity towards cathepsin L, highlighting its potential for further investigation in treating COVID-19.

CHEMMEDCHEM (2022)

Review Biochemistry & Molecular Biology

COVID-19 vaccines: where we stand and challenges ahead

Guido Forni et al.

Summary: The development of vaccines has made significant progress, but still faces various challenges, including different target populations, immunological adaptability of vaccines, and production and distribution issues. To ensure equitable access, protection of diverse subjects, and immunity against viral variants, multiple vaccines may be needed in the long run.

CELL DEATH AND DIFFERENTIATION (2021)

Article Chemistry, Medicinal

A Quick Route to Multiple Highly Potent SARS-CoV-2 Main Protease Inhibitors**

Kai S. Yang et al.

Summary: This study developed a series of SARS-CoV-2 main protease inhibitors with high potency by forming reversible covalent bonds with the active site cysteine C145, showing potential as COVID-19 treatment options. The most potent compound, MPI3, demonstrated a Ki value of 8.3 nM. Inhibitor MPI5 and MPI8 completely prevented SARS-CoV-2-induced cytopathogenic effect in cells at low concentrations, surpassing some existing molecules under clinical investigation for COVID-19 treatment. Further exploration of chemical space is needed to develop SC2M(Pro) inhibitors with ultra-high antiviral potency.

CHEMMEDCHEM (2021)

Article Biochemistry & Molecular Biology

Human SARS CoV-2 spike protein mutations

Lalitha Guruprasad

Summary: Analyzing spike protein sequences from different regions globally, this study found that out of 10333 sequences, 8155 proteins had mutations. A total of 9654 mutations were observed, with 44 mutations in the RBD region.

PROTEINS-STRUCTURE FUNCTION AND BIOINFORMATICS (2021)

Article Microbiology

Hydroxychloroquine-mediated inhibition of SARS-CoV-2 entry is attenuated by TMPRSS2

Tianling Ou et al.

Summary: Chloroquine and hydroxychloroquine have been shown to inhibit viral infection by targeting different pathways through which the SARS-CoV-2 spike protein is activated. SARS-CoV-2 relies more on the TMPRSS2 pathway for entry, while the presence of a furin-cleavage site in its spike protein further complicates the treatment with hydroxychloroquine alone. Combining hydroxychloroquine with a TMPRSS2 inhibitor may provide a more effective strategy to block SARS-CoV-2 infection.

PLOS PATHOGENS (2021)

Article Multidisciplinary Sciences

A drug repurposing screen identifies hepatitis C antivirals as inhibitors of the SARS-CoV2 main protease

Jeremy D. Baker et al.

Summary: Effective SARS-CoV-2 antiviral drugs are urgently needed, and study identified existing drugs with potential for therapeutic repurposing against SARS-CoV-2. The findings suggest that previous drug development initiatives targeting hepatitis C NS3/4A viral protease should be reconsidered, as some compounds may be more potent against SARS-CoV-2 Mpro than boceprevir.

PLOS ONE (2021)

Article Multidisciplinary Sciences

Bepridil is potent against SARS-CoV-2 in vitro

Erol C. Vatansever et al.

Summary: Through computational docking analysis, several FDA/EMA-approved drugs were found to inhibit the main protease of SARS-CoV-2, with three drugs showing strong antiviral activity by interfering with viral entry into host cells and inhibiting viral proteins in infected cells, especially bepridil demonstrating significant anti-SARS-CoV-2 activity in cell experiments.

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

Letter Multidisciplinary Sciences

Dipyridamole, chloroquine, montelukast sodium, candesartan, oxytetracycline, and atazanavir are not SARS-CoV-2 main protease inhibitors

Chunlong Ma et al.

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA (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 Biochemistry & Molecular Biology

A Clinical-Stage Cysteine Protease Inhibitor blocks SARS-CoV-2 Infection of Human and Monkey Cells

Drake M. Mellott et al.

Summary: K777, an irreversible inactivator of cysteine proteases, has shown reduction in the infectivity of SARS-CoV-2 in various host cells. By inhibiting the activity of host cathepsin L, this drug prevents the processing of viral spike protein, thereby reducing viral infectivity.

ACS CHEMICAL BIOLOGY (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)

Correction Multidisciplinary Sciences

Lead compounds for the development of SARS-CoV-2 3CL protease inhibitors (vol 12, 2016, 2021)

Sho Iketani et al.

NATURE COMMUNICATIONS (2021)

Letter Infectious Diseases

SARS-CoV-2 spike E484K mutation reduces antibody neutralisation

Sonia Jangra et al.

LANCET MICROBE (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

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)

Article Multidisciplinary Sciences

Identify potent SARS-CoV-2 main protease inhibitors via accelerated free energy perturbation-based virtual screening of existing drugs

Zhe Li et al.

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

Article Multidisciplinary Sciences

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

Lifeng Fu et al.

NATURE COMMUNICATIONS (2020)

Article Immunology

The Calcium Channel Blocker Bepridil Demonstrates Efficacy in the Murine Model of Marburg Virus Disease

Lisa Evans DeWald et al.

JOURNAL OF INFECTIOUS DISEASES (2018)

Article Biochemistry & Molecular Biology

A Genetically Encoded FRET Sensor for Intracellular Heme

Yanqun Song et al.

ACS CHEMICAL BIOLOGY (2015)

Article Chemistry, Medicinal

Design, synthesis and antiviral efficacy of a series of potent chloropyridyl ester-derived SARS-CoV 3CLpro inhibitors

Arun K. Ghosh et al.

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS (2008)

Article Biochemistry & Molecular Biology

A structural view of the inactivation of the SARS coronavirus main proteinase by benzotriazole esters

Koen H. G. Verschueren et al.

CHEMISTRY & BIOLOGY (2008)