Related Experiment Video

Updated: Oct 2, 2025

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

14.0K

Identifying Inhibitors of -1 Programmed Ribosomal Frameshifting in a Broad Spectrum of Coronaviruses

Sneha Munshi1, Krishna Neupane1, Sandaru M Ileperuma1

  • 1Department of Physics, University of Alberta, Edmonton, AB T6G 2E1, Canada.

Viruses
|February 26, 2022
PubMed

Insights

Researchers identified small-molecule inhibitors targeting programmed ribosomal frameshifting (-1 PRF) in coronaviruses (CoVs). These inhibitors show potential for broad-spectrum therapeutics against diverse CoVs, including bat CoVs, by targeting viral mRNA frameshift signals.

Area of Science:

  • Virology
  • Drug Discovery
  • Molecular Biology

Background:

  • Recurrent zoonotic coronavirus (CoV) outbreaks necessitate broad-spectrum therapeutics.
  • Programmed ribosomal frameshifting (-1 PRF) is a conserved mechanism in CoV replication, making its regulatory elements a potential drug target.

Purpose of the Study:

  • To investigate if small-molecule inhibitors of SARS-CoV-2 -1 PRF exhibit activity against a range of bat CoVs and MERS-CoV.
  • To validate viral mRNA frameshift signals as a viable target for pan-coronaviral therapeutics.

Main Methods:

  • Evaluation of six SARS-CoV-2 -1 PRF inhibitors against frameshift signals from various bat CoVs and MERS-CoV.
  • Utilized negative control viruses to assess specificity of inhibitor activity.

Main Results:

  • Some inhibitors demonstrated potent activity against specific subsets of CoV -1 PRF signals.
  • The serine protease inhibitor nafamostat significantly suppressed -1 PRF in multiple CoV frameshift signals.
  • Inhibitor activity was specific, with limited effects on negative control viruses.

Conclusions:

  • Small-molecule ligands can be developed to specifically inhibit -1 PRF across a broad spectrum of CoVs.
  • Viral frameshift signals represent a promising and viable target for the development of pan-coronaviral therapeutics.
Keywords:
SARS-CoV-2coronavirusprogrammed ribosomal frameshiftingtherapeuticstranslation

More Related Videos

Early Viral Entry Assays for the Identification and Evaluation of Antiviral Compounds09:29

Early Viral Entry Assays for the Identification and Evaluation of Antiviral Compounds

Published on: October 29, 2015

30.4K
Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors10:29

Quantitative Structure-Activity Relationship, Activity Prediction, and Molecular Dynamics of Non-nucleotide Reverse Transcriptase Inhibitors

Published on: May 9, 2025

1.6K

Related Concept Videos

Leaky Scanning02:28

Leaky Scanning

During most eukaryotic translation processes, the small 40S ribosome subunit scans an mRNA from its 5' end until it encounters the first start AUG codon. The large 60S ribosomal subunit then joins the smaller one to initiate protein synthesis. The location of the translation initiation is largely determined by the nucleotides near the start codon as there may be multiple translation initiation sites present on the mRNA.  Marilyn Kozak discovered that the sequence RCCAUGG (where R...
5.3K
Eukaryotic Transcription Inhibitors01:52

Eukaryotic Transcription Inhibitors

Certain biochemical processes, such as embryonic development and cell growth regulation, depend on the repression of specific genes. DNA binding proteins known as eukaryotic transcription inhibitors regulate the repression of gene expression in eukaryotes. The presence of these inhibitors at the required location and time in the cell is triggered by the presence of hormones and additional signals from other cells.
Eukaryotic transcription inhibitors usually contain two distinct domains, a...
10.1K
Viruses with RNA Genomes01:29

Viruses with RNA Genomes

RNA viruses are categorized into positive-strand, negative-strand, or double-stranded groups based on their genomic structure and replication mechanisms. This classification dictates how they exploit host cellular machinery for protein synthesis and replication. Some RNA viruses also utilize reverse transcription as part of their life cycle, further diversifying their replication strategies.Positive-Strand RNA VirusesPositive-strand RNA viruses have genomes that function directly as messenger...
187
RNA Interference01:23

RNA Interference

RNA interference (RNAi) is a process in which a small non-coding RNA molecule blocks the post-transcriptional expression of a gene by binding to its messenger RNA (mRNA) and preventing the protein from being translated.
This process occurs naturally in cells, often through the activity of genomically-encoded microRNAs. Researchers can take advantage of this mechanism by introducing synthetic RNAs to deactivate specific genes for research or therapeutic purposes. For example, RNAi could be used...
26.6K
Types of RNA01:23

Types of RNA

Overview
Three main types of RNA are involved in protein synthesis: messenger RNA (mRNA), transfer RNA (tRNA), and ribosomal RNA (rRNA). These RNAs perform diverse functions and can be broadly classified as protein-coding or non-coding RNA. Non-coding RNAs play important roles in the regulation of gene expression in response to developmental and environmental changes. Non-coding RNAs in prokaryotes can be manipulated to develop more effective antibacterial drugs for human or animal use.
RNA...
69.0K
Ribozymes02:47

Ribozymes

The term ribozyme is used for RNA that can act as an enzyme. Ribozymes are mainly found in selected viruses, bacteria, plant organelles, and lower eukaryotes. Ribozymes were first discovered in 1982 when Tom Cech’s laboratory observed Group I introns acting as enzymes. This was shortly followed by the discovery of another ribozyme, Ribonulcease P, by Sid Altman’s laboratory. Both Cech and Altman received the Nobel Prize in chemistry in 1989 for their work on ribozymes.
Ribozymes can...
12.7K