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Related Concept Videos

Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
Enzyme Inhibition01:30

Enzyme Inhibition

Inhibitors are molecules that reduce enzyme activity by binding to the enzyme. In a normally functioning cell, enzymes are regulated by a variety of inhibitors. Drugs and other toxins can also inhibit enzymes. Some inhibitors bind to the enzyme’s active site, while others inhibit enzymatic activity by binding to other sites on the protein structure.

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Updated: May 10, 2026

High-throughput Antiviral Assays to Screen for Inhibitors of Zika Virus Replication
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High-throughput Antiviral Assays to Screen for Inhibitors of Zika Virus Replication

Published on: October 30, 2021

Inhibitors Targeting SARS-CoV-2 Papain-Like Protease: Screening, Design, Synthesis, and Biological Evaluation.

Elena-Oriana Iuga1,2, Nilu Gone1,2, Mariana Ortiz de Godoy3

  • 1Institute of Pharmacy, Pharmaceutical/Medicinal Chemistry, Eberhard Karls University, Tübingen, Germany.

Chemmedchem
|May 9, 2026
PubMed
Summary

New SARS-CoV-2 papain-like protease (PLpro) inhibitors were developed. Compound 2t showed potent antiviral activity without toxicity, making it a promising candidate for future drug development against COVID-19.

Keywords:
COVID‐19SARS‐CoV‐2antiviralnon‐covalent inhibitorspapain‐like protease

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High-throughput Screening for Broad-spectrum Chemical Inhibitors of RNA Viruses
11:34

High-throughput Screening for Broad-spectrum Chemical Inhibitors of RNA Viruses

Published on: May 5, 2014

Related Experiment Videos

Last Updated: May 10, 2026

High-throughput Antiviral Assays to Screen for Inhibitors of Zika Virus Replication
10:16

High-throughput Antiviral Assays to Screen for Inhibitors of Zika Virus Replication

Published on: October 30, 2021

High-throughput Screening for Broad-spectrum Chemical Inhibitors of RNA Viruses
11:34

High-throughput Screening for Broad-spectrum Chemical Inhibitors of RNA Viruses

Published on: May 5, 2014

Area of Science:

  • Virology
  • Drug Discovery
  • Biochemistry

Background:

  • Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) remains a global health concern, necessitating novel therapeutic strategies.
  • The SARS-CoV-2 papain-like protease (PLpro) is crucial for viral replication and immune evasion, representing a key target for antiviral development.

Purpose of the Study:

  • To identify and characterize novel non-covalent and covalent inhibitors of SARS-CoV-2 PLpro.
  • To evaluate the antiviral efficacy and safety of identified PLpro inhibitors.

Main Methods:

  • Design and synthesis of non-covalent PLpro inhibitors based on GRL0617.
  • Screening of an in-house library for covalent PLpro inhibitors.
  • Biochemical assays to determine inhibitory activity (IC50) and antiviral assays (EC50).
  • Molecular modeling for binding interaction analysis.

Main Results:

  • Non-covalent inhibitor 2t demonstrated potent PLpro inhibition (IC50 = 0.634 µM) and significant antiviral activity (EC50 = 2.89 µM) without cellular toxicity.
  • Covalent inhibitors 13e and 13f also showed promising PLpro inhibition (IC50 = 22.0 µM and 5.0 µM, respectively).
  • Molecular modeling indicated stable binding of 2t within the PLpro active site.

Conclusions:

  • Compound 2t is a highly effective non-covalent SARS-CoV-2 PLpro inhibitor with demonstrated antiviral properties and a favorable safety profile.
  • 2t represents a promising lead compound for the development of new antiviral therapies against SARS-CoV-2 infections.