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Related Concept Videos

Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

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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...
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Leaky Scanning

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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...
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siRNA - Small Interfering RNAs02:30

siRNA - Small Interfering RNAs

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Small interfering RNAs, or siRNAs, are short regulatory RNA molecules that can silence genes post-transcriptionally, as well as the transcriptional level in some cases. siRNAs are important for protecting cells against viral infections and silencing transposable genetic elements.
In the cytoplasm, siRNA is processed from a double-stranded RNA, which comes from either endogenous DNA transcription or exogenous sources like a virus. This double-stranded RNA is then cleaved by the...
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Inhibitors of Bacterial Protein Synthesis01:25

Inhibitors of Bacterial Protein Synthesis

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Aminoglycosides constitute a highly potent class of bactericidal antibiotics that exert their antimicrobial effects by targeting the bacterial ribosome, specifically disrupting protein synthesis. These polycationic molecules consist of amino-modified sugars linked via glycosidic bonds to an aminocyclitol core such as 2-deoxystreptamine or streptamine. Their strong positive charges facilitate tight binding to the negatively charged phosphate backbone of ribosomal RNA (rRNA), primarily at the 16S...
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Types of RNA01:23

Types of RNA

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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...
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Subviral Agents01:29

Subviral Agents

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Subviral agents are infectious entities that resemble viruses but lack one or more viral components, such as a capsid or essential replication machinery. These agents include viroids, prions, and satellites, each possessing distinct structural and functional characteristics that influence their mode of infection and replication.Viroids are the simplest subviral agents, consisting of circular, single-stranded RNA molecules without a protein coat. They exclusively infect plants, relying entirely...
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Related Experiment Video

Updated: Apr 5, 2026

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

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SARS-CoV-2 Antivirals Identified from Small Molecule Modulators of Programmed -1 Ribosomal Frameshifting.

Emily G Swanson Hay1, Madison M Maille2, Martina Zafferani1

  • 1Department of Chemistry, Duke University, 124 Science Drive, Durham, North Carolina 27708, United States.

ACS Infectious Diseases
|April 3, 2026
PubMed
Summary

Researchers identified novel small molecules targeting the SARS-CoV-2 RNA pseudoknot to inhibit viral replication. This approach expands COVID-19 treatment options by targeting conserved viral RNA structures, offering a promising new antiviral strategy.

Keywords:
RNASARS-CoV-2antiviralsframeshiftingpseudoknotsmall molecules

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

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Area of Science:

  • Virology
  • Medicinal Chemistry
  • Molecular Biology

Background:

  • Emerging SARS-CoV-2 variants and waning immunity necessitate new antiviral treatments.
  • Targeting conserved viral RNA structures offers an alternative to protein-based therapeutics.
  • Modulating programmed -1 ribosomal frameshifting (-1 PRF) can inhibit coronavirus replication.

Purpose of the Study:

  • To identify small molecules that inhibit SARS-CoV-2 replication by targeting the frameshift site pseudoknot.
  • To evaluate the efficacy and mechanism of action of identified small molecules.

Main Methods:

  • Screening of an RNA-biased synthetic small molecule library against the SARS-CoV-2 frameshift pseudoknot.
  • In vitro and in cellulo assays to assess frameshift inhibition and viral replication.
  • RT-qPCR assays to measure pseudoknot stability and RNA binding studies.

Main Results:

  • Seven candidate molecules demonstrated dose-dependent inhibition of -1 PRF and SARS-CoV-2 replication in cell culture.
  • Binding to the pseudoknot was necessary but did not correlate with frameshift inhibition efficacy.
  • Pseudoknot stability changes did not predict frameshift efficiency modulation.

Conclusions:

  • Small molecules targeting the SARS-CoV-2 frameshift pseudoknot are promising antiviral candidates.
  • Multiple characterization methods are crucial for evaluating small molecule-RNA interactions.
  • The complexity of targeting dynamic RNA structures requires early functional screening and later optimization of the mode of action.