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Related Concept Videos

Transfer RNA Synthesis02:36

Transfer RNA Synthesis

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One of the unique features of tRNA is the presence of modified bases. In some tRNAs, modified bases account for nearly 20% of the total bases in the molecule. Altogether, these unusual bases protect the tRNA from enzymatic degradation by RNases.
Each of these chemical modifications is carried by a specific enzyme, post-transcription. All of these enzymes have unique base and site-specificity. Methylation, the most common chemical modification, is carried by at least nine different enzymes, with...
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Transfer RNA Synthesis

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Initiation of Translation02:33

Initiation of Translation

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Initiating translation is complex because it involves multiple molecules. Initiator tRNA, ribosomal subunits, and eukaryotic initiation factors (eIFs) are all required to assemble on the initiation codon of mRNA. This process consists of several steps that are mediated by different eIFs.
First, the initiator tRNA must be selected from the pool of elongator tRNAs by eukaryotic initiation factor 2 (eIF2). The initiator tRNA (Met-tRNAi) has conserved sequence elements including modified bases at...
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Leaky Scanning02:28

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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tRNA Activation02:26

tRNA Activation

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Aminoacyl-tRNA synthetases are present in both eukaryotes and bacteria. Though eukaryotes have 20 different aminoacyl-tRNA synthetases to couple to 20 amino acids, many bacteria do not have genes for all of these aminoacyl-tRNA synthetases. Despite this, they still use all 20 amino acids to synthesize their proteins. For instance, some bacteria do not have the gene encoding the enzyme that couples glutamine with its partner tRNA. In these organisms, one enzyme adds glutamic acid to all of the...
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Retrovirus Life Cycles01:10

Retrovirus Life Cycles

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Retroviruses have a single-stranded RNA genome that undergoes a special form of replication. Once the retrovirus has entered the host cell, an enzyme called reverse transcriptase synthesizes double-stranded DNA from the retroviral RNA genome. This DNA copy of the genome is then integrated into the host’s genome inside the nucleus via an enzyme called integrase. Consequently, the retroviral genome is transcribed into RNA whenever the host’s genome is transcribed, allowing the...
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Reverse Genetics Mediated Recovery of Infectious Murine Norovirus
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Prolyl tRNA Synthetase Is Required for Mammarenavirus Multiplication.

Haydar Witwit1, Pablo Ibanez1, Ruifeng Zhou1

  • 1Department of Immunology and Microbiology, The Scripps Research Institute, La Jolla, CA 92037, USA.

Viruses
|February 27, 2026
PubMed
Summary

Halofuginone (HF) demonstrates potent antiviral activity against dangerous mammarenaviruses (MaAv), including Lassa virus and Junin virus. This compound inhibits viral replication by targeting a key enzyme, offering a potential new treatment for these serious infections.

Keywords:
JUNVLASVLCMVbroad-spectrum antiviralshost-directed antiviralsmammarenavirusesprolyl-tRNA synthetase

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Area of Science:

  • Virology
  • Drug Discovery
  • Molecular Biology

Background:

  • Mammarenaviruses (MaAv), such as Lassa virus (LASV) and Junin virus (JUNV), cause severe human diseases and significant public health issues.
  • Lymphocytic choriomeningitis virus (LCMV), another MaAv, is an underrecognized pathogen, particularly risky for congenital infections and immunocompromised individuals.
  • Current treatments for MaAv infections are limited, with no FDA-approved vaccines or antivirals, and controversial efficacy of ribavirin.

Purpose of the Study:

  • To investigate the antiviral potential of Halofuginone (HF) against pathogenic mammarenaviruses (MaAv).
  • To elucidate the mechanism of action of HF in inhibiting MaAv replication.

Main Methods:

  • Dose-dependent antiviral assays were performed using LCMV, LASV, and JUNV.
  • The interaction of HF with glutamyl-prolyl-tRNA synthetase 1 (EPRS1) was analyzed.
  • The effect of HF on viral entry, virus ribonucleoprotein (vRNP) activity, and Z budding was assessed.
  • Experiments included the addition of exogenous proline to evaluate its impact on HF's antiviral activity.

Main Results:

  • HF exhibited potent, dose-dependent antiviral activity against LCMV, LASV, and JUNV.
  • HF inhibits the prolyl-tRNA synthetase (PRS) activity of EPRS1, leading to translation inhibition via amino acid starvation.
  • The antiviral effect of HF was confirmed by proline supplementation, indicating the critical role of PRS inhibition.
  • HF strongly inhibited (>90%) viral Z budding activity, a crucial step in viral release.

Conclusions:

  • Halofuginone (HF) is a promising antiviral agent against pathogenic mammarenaviruses (MaAv).
  • HF's mechanism involves the inhibition of prolyl-tRNA synthetase (PRS) activity, impacting viral protein synthesis and budding.
  • Further development of HF or its derivatives could lead to novel therapeutics for MaAv infections.