Discovery of Potent Pyrazoline-Based Covalent SARS-CoV-2 Main Protease Inhibitors

Article Multidisciplinary Sciences

Defining the substrate envelope of SARS-CoV-2 main protease to predict and avoid drug resistance

Ala M. Shaqra et al.

Summary: The study determined the crystal structures of SARS-CoV-2 main protease (Mpro) bound to substrate peptides, defining the substrate envelope and identifying sites susceptible to drug resistance. These findings provide insights for developing robust inhibitors against SARS-CoV-2 and preventing drug resistance.

NATURE COMMUNICATIONS (2022)

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Article Biology

Comprehensive fitness landscape of SARS-CoV-2 M-pro reveals insights into viral resistance mechanisms

Julia M. Flynn et al.

Summary: The evolution of pathogens necessitates effective antiviral drugs, with drug design targeting the SARS-CoV-2 main protease (M-pro) showing promise and progress in identifying mutation sites resistant to drugs.

ELIFE (2022)

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Editorial Material Multidisciplinary Sciences

A white-knuckle ride of open COVID drug discovery

Frank von Delft et al.

NATURE (2021)

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Article Biochemistry & Molecular Biology

An automatic pipeline for the design of irreversible derivatives identifies a potent SARS-CoV-2 Mpro inhibitor

Daniel Zaidman et al.

Summary: The computational pipeline presented in this study identifies irreversible inhibitors that can bind covalently to cysteine, showing promise for drug development in recent prospective evaluations.

CELL CHEMICAL BIOLOGY (2021)

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Article Biochemistry & Molecular Biology

Chemoproteomics-enabled discovery of covalent RNF114-based degraders that mimic natural product function

Mai Luo et al.

Summary: This study found that the natural product nimbolide can be used as a recruiter of the E3 ubiquitin ligase RNF114 for targeted protein degradation, which is important in modern drug discovery. Through activity-based protein profiling-enabled ligand screening, fully synthetic molecules mimicking nimbolide were discovered, showing potential for degrading therapeutic targets.

CELL CHEMICAL BIOLOGY (2021)

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Article Multidisciplinary Sciences