French Team Identifies Antidote for Ricin Toxin

A large team of French researchers has discovered two low molecular weight compounds that block the action of ricin, a highly toxic protein often mentioned as a possible bioterror weapon.

Ricin comprises two subunits, the A-chain and the B-chain, which are linked by a disulphide bond. The B-chain facilitates cell entry and intracellular transport, and it is reductively cleaved to free the A-chain, which inactivates ribosomes and shuts down protein synthesis.

A French team, headed by investigators at the Centre National de la Recherche Scientifique (Paris, France) used a cell-based assay system to screen over 16,000 compounds for the ability to block the intracellular transport of ricin toxins.

They reported in the April 16, 2010, online edition of the journal Cell that they had identified two compounds, Retro-1 and Retro-2 that were able to inhibit the retrograde transport route of ricin from the plasma membrane to the endoplasmic reticulum. Unlike other compounds that are known to block retrograde transport, Retro-1 and Retro-2 did not affect other intracellular trafficking and did not show any toxicity.

In experiments in mice, Retro-2 was shown to block the activity of ricin, if it were given prior to the toxin. It is expected that these compounds should also inhibit other toxic proteins such as the Shiga-like toxins produced by pathogens such as E. coli, Shigella, and cholera.

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Centre National de la Recherche Scientifique