Related Experiment Video

Updated: Jun 27, 2026

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules
10:58

Protein WISDOM: A Workbench for In silico De novo Design of BioMolecules

Published on: July 25, 2013

Design and characterization of an HIV-specific ribonuclease zymogen

Rebecca F Turcotte1, Ronald T Raines

  • 1Medical Scientist Training Program and Biophysics Graduate Program, University of Wisconsin-Madison, Madison, Wisconsin 53706, USA.

AIDS Research and Human Retroviruses
|November 26, 2008
PubMed

Insights

Researchers developed a novel antiviral by modifying bovine pancreatic ribonuclease (RNase A). This RNase A zymogen is activated by human immunodeficiency virus (HIV) protease, offering a new strategy for HIV/AIDS treatment.

Area of Science:

  • Biochemistry
  • Virology
  • Drug Discovery

Background:

  • Ribonucleases (RNases) exhibit cytotoxic activity, leading to interest in their therapeutic potential.
  • Ranpirnase, an amphibian RNase, is in clinical trials for cancer treatment.
  • Mammalian RNases like bovine pancreatic ribonuclease (RNase A) are homologous to ranpirnase.

Purpose of the Study:

  • To create a novel antiviral agent based on RNase A.
  • To develop an agent targeting human immunodeficiency virus (HIV).
  • To explore a new therapeutic strategy for HIV/AIDS.

Main Methods:

  • Linking the N- and C-termini of RNase A with an HIV protease-cleavable sequence.
  • Creating an inactive RNase A zymogen.
  • Assessing the effect of HIV-1 protease cleavage on RNase activity.

Main Results:

  • The engineered RNase A functions as an HIV-specific zymogen.
  • Cleavage by HIV-1 protease activates RNase A, increasing its activity 50-fold.
  • The approach relies on HIV-1 protease function, potentially avoiding resistance.

Conclusions:

  • A novel RNase A-based zymogen was successfully created.
  • This strategy offers a new class of antiviral agents targeting HIV/AIDS.
  • The mechanism circumvents known resistance pathways by utilizing viral protease activity.

More Related Videos

Analysis of Group IV Viral SSHHPS Using In Vitro and In Silico Methods10:40

Analysis of Group IV Viral SSHHPS Using In Vitro and In Silico Methods

Published on: December 21, 2019

Evaluation of the Efficacy And Toxicity of RNAs Targeting HIV-1 Production for Use in Gene or Drug Therapy12:03

Evaluation of the Efficacy And Toxicity of RNAs Targeting HIV-1 Production for Use in Gene or Drug Therapy

Published on: September 5, 2016

Related Concept Videos

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 be...
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 be...
Inhibitors of Virion Maturation and Assembly01:19

Inhibitors of Virion Maturation and Assembly

As part of their replication cycle, certain viruses synthesize long precursor proteins called polyproteins within infected host cells. In human immunodeficiency virus (HIV), two major polyproteins are produced: Gag and Gag-Pol. The Gag polyprotein supplies the structural components of the virus, while Gag-Pol includes essential viral enzymes such as reverse transcriptase, integrase, and protease. After synthesis, these polyproteins move to the host cell membrane, where they assemble into an...
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 stands for...