A synthetic HIV-1 protease inhibitor with antiviral activity arrests HIV-like particle maturation

Article Abstract:

After the AIDS virus (HIV) directs its host cell to synthesize viral proteins, these proteins must be assembled into new virus particles (virions). At least two viral proteins, encoded by the pol and gag genes, need to be processed before the assembly of the virus can proceed. This processing is accomplished by the aspartic protease produced by the virus' HIV-1 gene. Although most major research efforts against AIDS have been directed at reverse transcriptase (which helps the viral genes to reproduce) or CD4, which is the molecule on human cells to which the infectious virion attaches, researchers have now shown that at least in tissue culture it is possible to inhibit the maturation of virus particles by inhibiting the protease necessary for their assembly. The inhibitor is a synthetic molecule that is almost like the proteins which are the normal targets of the HIV protease, but the synthetic molecule contains a pseudodipeptidyl insert where the protease would normally split the molecule. Unlike the normal peptide bond which holds together natural proteins, the synthetic insert stymies the viral protease and renders it ineffective. Once inactivated, the protease cannot participate in the assembly of new virions. The type of synthetic compound used has been shown to be nontoxic, but it has not yet been shown if this substance can inhibit the AIDS virus in humans. In addition, since other proteases exist in the body and are essential for normal function, it is not yet clear whether the effective dose concentration used in tissue culture studies can be maintained in animals or people. (Consumer Summary produced by Reliance Medical Information, Inc.)

Antiviral agents

---

Conserved folding in retroviral proteases: crystal structure of a synthetic HIV-1 protease

Article Abstract:

The design of drugs to attack the biochemical action of viral enzymes depends on the three-dimensional structure of these compounds. This can be only obtained through crystallographic analysis of purified crystalline preparations of the enzymes. The crystalline structure of a chemically synthesized protease (whose function is to split and join proteins) derived from the human immunodeficiency virus (HIV-1 protease) has been determined. The work was based on previously prepared model structures of proteases derived from the Rous sarcoma virus, an animal virus. The enzyme is essential for the assemblage of proteins into larger polyproteins that must be replicated to allow the proliferation of the HIV-1 virus. This enzyme is, therefore, considered essential for replication and infection. It is also an attractive target for agents designed to prevent replication. The study describes images of the three-dimensional structure of the enzyme, which is found to be contain 99 amino acids. The structure of this enzyme has been previously reported, but the current report details several important corrections to the structure outlined in the previous report. The enzyme is made of two identical subunits which form the active structure (a dimer). The interface between the two identical segments is described. The structure, taken as a whole, presents possible sites for the design of agents to neutralize its function.

Genetic aspects, Crystals, Retroviruses

---

Hats off the the tricorn protease

Article Abstract:

Tomohiro Tamura et al have found a new proteolytic structure in the Thermophilic Archaebacterium Thermoplasma acidophilum, called TRI for its tricorn shape, which acts separately from the organism's proteasome. Its structure and suspected function are described.

Archaeabacteria, Archaea

Similar abstracts:

• Abstracts: Yeast prions: DNA-free genetics? Yeast protein acting alone triggers prion-like process. Gaps in starbirth picture filled
• Abstracts: Opening the way to gene activity. How male animals gain an edge in the mating game
• Abstracts: Monitoring soil column mobility of cross-linked and soluble polyacrylates using gel permeation chromatography
• Abstracts: A support system for multiple perspectives knowledge management and conflict resolution. Experiences with facilitating policy meetings with group support systems
• Abstracts: Real-time characterization of the organic composition and size of individual diesel engine smoke particles. A partition-limited model for the plant uptake of organic contaminants from soil and water

This website is not affiliated with document authors or copyright owners. This page is provided for informational purposes only. Unintentional errors are possible.