Ricin

Ricin (/ˈraɪsɪn/ RY-sin) is a lectin (a carbohydrate-binding protein) and a highly potent toxin produced in the seeds of the castor oil plant, Ricinus communis.

Type 2 RIPs consist of an A chain that is functionally equivalent to a type 1 RIP, covalently connected by a single disulfide bond to a B chain that is catalytically inactive, but serves to mediate transport of the A-B protein complex from the cell surface, via vesicle carriers, to the lumen of the endoplasmic reticulum (ER).

[8] Ricin B chain binds complex carbohydrates on the surface of eukaryotic cells containing either terminal N-acetylgalactosamine or beta-1,4-linked galactose residues.

[13] Ricin molecules are thought to follow retrograde transport via early endosomes, the trans-Golgi network, and the Golgi to enter the lumen of the endoplasmic reticulum (ER).

[24] RTA specifically and irreversibly hydrolyses the N-glycosidic bond of the adenine residue at position 4324 (A4324) within the 28S rRNA, but leaves the phosphodiester backbone of the RNA intact.

Within the active site of RTA, there exist several invariant amino acid residues involved in the depurination of ribosomal RNA.

The model proposed by Mozingo and Robertus,[6] based on X-ray structures, is as follows: Ricin is very toxic if inhaled, injected, or ingested.

[29][30] Because the symptoms are caused by failure to make protein, they may take anywhere from hours to days to appear, depending on the route of exposure and the dose.

The low blood volume (hypovolemia) caused by gastrointestinal fluid loss can lead to organ failure in the pancreas, kidney, liver, and GI tract and progress to shock.

[31][32] As of 2005 another antidote developed by the US military has been shown to be safe and effective in lab mice injected with antibody-rich blood mixed with ricin, and has had some human testing.

Possible treatments include intravenous fluids or electrolytes, airway management, assisted ventilation, or giving medications to remedy seizures and low blood pressure.

In 1978 Bulgarian defector Vladimir Kostov survived a ricin attack similar to the one on Georgi Markov, probably due to his body's production of antibodies.

For this reason only small amounts of ricin had leaked out of the pellet, producing some symptoms but allowing his body to develop immunity to further poisoning.

[36] Accidental ingestion of Ricinus communis cake intended for fertilizer has been reported to be responsible for fatal ricin poisoning in animals.

[39] Rauber and Heard have written that close examination of early 20th century case reports indicates that public and professional perceptions of ricin toxicity "do not accurately reflect the capabilities of modern medical management".

[42] Victims often manifest nausea, diarrhea, fast heart rate, low blood pressure, and seizures persisting for up to a week.

A promising approach for ricin is to use the non-toxic B subunit (a lectin) as a vehicle for delivering antigens into cells, thus greatly increasing their immunogenicity.

[46] Ricin is classified as an extremely hazardous substance in the United States as defined in Section 302 of the US Emergency Planning and Community Right-to-Know Act (42 U.S.C.

[citation needed] Interest in it continued for a short period after World War II, but soon subsided when the US Army Chemical Corps began a program to weaponize sarin.

Jan van Aken, a German expert on biological weapons, explained in a report for The Sunshine Project that Al Qaeda's experiments with ricin suggest their inability to produce botulinum or anthrax.

Two recombinant A subunit (RTA)-based vaccines, RiVax and RVEc (also known as RTA1-33/44-198),[59][60] have completed Phase I clinical trials, and were found to be safe.

[61] These vaccines are based on modified versions of the ricin toxin A-chain, designed to reduce toxicity while maintaining immunogenicity.

Grants from the National Institute of Allergy and Infectious Diseases and the US Food and Drug Administration supported development of the vaccine candidate.

[29][68] He died in a hospital a few days later; his body was passed to a special poison branch of the British Ministry of Defence that discovered the pellet during an autopsy.

[71] Another was sent to the offices of Mayors Against Illegal Guns in Washington, D.C. A letter containing ricin was also reported to have been sent to American President Barack Obama at the same time.

Shannon Richardson, an actress, was later charged with the crime, and pleaded guilty that December;[72] she was sentenced to 18 years in prison plus a restitution fine of US$367,000.

[73] On 2 October 2018, two letters suspected of containing ricin were sent to The Pentagon, one addressed to Secretary of Defense James Mattis, and the other to Chief of Naval Operations, Admiral John Richardson.

[75] In 2020, some media in the Czech Republic reported, based on intelligence information, that a person carrying a Russian diplomatic passport and ricin had arrived in Prague with the intention of assassinating three politicians.

[76][77] Czech president Miloš Zeman later described the police protection of Zdeněk Hřib as an attempt by an insignificant politician to gain attention.

[83] Mohammed Ali from Liverpool, England, was convicted after attempting to purchase 500 mg of ricin over the dark web from an undercover FBI agent.

A comparison of the similar structures of abrin-a (red) and ricin (blue)
Castor beans
Castor oil seeds in the Royal Botanic Gardens, Kew Economic Botany Collection
A metal vial containing ricin from the 2003 ricin letters
Ricin toxin, RiVax, RTA1-33/44-198, and a single domain antibody-antigen complex with the RTA1-33/44-198 immunogen. Original figure can be found in Legler, et al. [ 57 ] [ 58 ]