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Mini-Reviews in Medicinal Chemistry

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ISSN (Print): 1389-5575
ISSN (Online): 1875-5607

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Review Article

The Search for Antidotes Against Ricin

Author(s): Fernanda Diniz Botelho, Tanos Celmar Costa Franca* and Steven R. LaPlante*

Volume 24, Issue 12, 2024

Published on: 23 January, 2024

Page: [1148 - 1161] Pages: 14

DOI: 10.2174/0113895575270509231121060105

Price: $65

Abstract

The castor plant (Ricinus communis) is primarily known for its seeds, which contain a unique fatty acid called ricinoleic acid with several industrial and commercial applications. Castor seeds also contain ricin, a toxin considered a chemical and biological warfare agent. Despite years of investigation, there is still no effective antidote or vaccine available. However, some progress has been made, and the development of an effective treatment may be on the horizon. To provide an updated overview of this issue, we have conducted a comprehensive review of the literature on the current state of research in the fight against ricin. This review is based on the reported research and aims to address the challenges faced by researchers, as well as highlight the most successful cases achieved thus far. Our goal is to encourage the scientific community to continue their efforts in this critical search.

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Graphical Abstract

[1]
Zhou, K.; Fu, Z.; Chen, M.; Lin, Y.; Pan, K. Structure of trichosanthin at 1.88 Å resolution. Proteins, 1994, 19(1), 4-13.
[http://dx.doi.org/10.1002/prot.340190103] [PMID: 8066085]
[2]
Funatsu, G.; Islam, M.R.; Minami, Y.; Sung-Sil, K.; Kimura, M. Conserved amino acid residues in ribosome-inactivating proteins from plants. Biochimie, 1991, 73(7-8), 1157-1161.
[http://dx.doi.org/10.1016/0300-9084(91)90160-3] [PMID: 1742358]
[3]
Endo, Y.; Tsurugi, K.; Yutsudo, T.; Takeda, Y.; Ogasawara, T.; Igarashi, K. Site of action of a Vero toxin (VT2) from Escherichia coli O157:H7 and of Shiga toxin on eukaryotic ribosomes. Eur. J. Biochem., 1988, 171(1-2), 45-50.
[http://dx.doi.org/10.1111/j.1432-1033.1988.tb13756.x] [PMID: 3276522]
[4]
May, M.J.; Hartley, M.R.; Roberts, L.M.; Krieg, P.A.; Osborn, R.W.; Lord, J.M. Ribosome inactivation by ricin A chain: A sensitive method to assess the activity of wild-type and mutant polypeptides. EMBO J., 1989, 8(1), 301-308.
[http://dx.doi.org/10.1002/j.1460-2075.1989.tb03377.x] [PMID: 2714255]
[5]
Janik, E.; Ceremuga, M.; Saluk-Bijak, J.; Bijak, M. Biological toxins as the potential tools for bioterrorism. Int. J. Mol. Sci., 2019, 20(5), 1181.
[http://dx.doi.org/10.3390/ijms20051181] [PMID: 30857127]
[6]
Patel, V.R.; Dumancas, G.G.; Viswanath, L.C.K.; Maples, R.; Subong, B.J.J. Castor oil: Properties, uses, and optimization of processing parameters in commercial production. Lipid Insights, 2016, 9, 1-12.
[http://dx.doi.org/10.4137/LPI.S40233]
[7]
Doan, L.G. Ricin: Mechanism of toxicity, clinical manifestations, and vaccine development. A review. J. Toxicol. Clin. Toxicol., 2004, 42(2), 201-208.
[http://dx.doi.org/10.1081/CLT-120030945] [PMID: 15214627]
[8]
Challoner, K.R.; McCarron, M.M. Castor bean intoxication. Ann. Emerg. Med., 1990, 19(10), 1177-1183.
[http://dx.doi.org/10.1016/S0196-0644(05)81525-2] [PMID: 2221525]
[9]
Balint, G.A. Ricin: The toxic protein of castor oil seeds. Toxicology, 1974, 2(1), 77-102.
[http://dx.doi.org/10.1016/0300-483X(74)90044-4] [PMID: 4823740]
[10]
Robb, J.G.; Laben, R.C.; Walker, H.G., Jr; Herring, V. Castor meal in dairy rations. J. Dairy Sci., 1974, 57(4), 443-450.
[http://dx.doi.org/10.3168/jds.S0022-0302(74)84912-X]
[11]
Lima, R.L.S.; Severino, L.S.; Sampaio, L.R.; Sofiatti, V.; Gomes, J.A.; Beltrão, N.E.M. Blends of castor meal and castor husks for optimized use as organic fertilizer. Ind. Crops Prod., 2011, 33(2), 364-368.
[http://dx.doi.org/10.1016/j.indcrop.2010.11.008]
[12]
Ebbecke, M.; Hünefeld, D.; Schaper, A.; Desl, H. Increasing frequency of serious or fatal poisonings in dogs caused by organic fertilizers during the summer of 2001 in Germany. Clin. Toxicol., 2002, 40, 346-347.
[13]
Lim, H.; Kim, H.J.; Cho, Y.S. A case of ricin poisoning following ingestion of Korean castor bean. Emerg. Med. J., 2009, 26(4), 301-302.
[http://dx.doi.org/10.1136/emj.2007.055368] [PMID: 19307402]
[14]
Wedin, G.P.; Neal, J.S.; Everson, G.W.; Krenzelok, E.P. Castor bean poisoning. Am. J. Emerg. Med., 1986, 4(3), 259-261.
[http://dx.doi.org/10.1016/0735-6757(86)90080-X] [PMID: 3964368]
[15]
Arnold, H.L. Poisoning from castor beans. Science, 1924, 59(1539), 577-577.
[http://dx.doi.org/10.1126/science.59.1539.577.b] [PMID: 17843137]
[16]
Targosz, D.; Winnik, L.; Szkolnicka, B. Suicidal poisoning with castor bean (Ricinus communis) extract injected subcutaneously: Case report. J. Toxicol. Clin. Toxicol., 2002, 40, 398.
[17]
Coopman, V.; De Leeuw, M.; Cordonnier, J.; Jacobs, W. Suicidal death after injection of a castor bean extract (Ricinus communis L.). Forensic Sci. Int., 2009, 189(1-3), e13-e20.
[http://dx.doi.org/10.1016/j.forsciint.2009.04.019] [PMID: 19477090]
[18]
Hutchinson, L.T.R. Poisoning by castor-oil seeds. Ind. Med. Gaz., 1900, 35(5), 196-197.
[PMID: 29003252]
[19]
Knight, B. Ricin--a potent homicidal poison. BMJ, 1979, 1(6159), 350-351.
[PMID: 421122]
[20]
Worbs, S.; Köhler, K.; Pauly, D.; Avondet, M.A.; Schaer, M.; Dorner, M.B.; Dorner, B.G. Ricinus communis intoxications in human and veterinary medicine-a summary of real cases. Toxins, 2011, 3(10), 1332-1372.
[http://dx.doi.org/10.3390/toxins3101332] [PMID: 22069699]
[21]
Audi, J.; Belson, M.; Patel, M.; Schier, J.; Osterloh, J. Ricin poisoning. JAMA, 2005, 294(18), 2342-2351.
[http://dx.doi.org/10.1001/jama.294.18.2342] [PMID: 16278363]
[22]
Pita, R.; Romero, A. Toxins as weapons: A historical review. Forensic Sci. Rev., 2014, 26(2), 85-96.
[PMID: 26227025]
[23]
Augerson, W. A review of the scientific literature as it pertains to gulf war illnesses. In: Chemical and Biological Warfare Agents; , 2000.
[http://dx.doi.org/10.7249/MR1018.5]
[24]
Jansen, H.J.; Breeveld, F.J.; Stijnis, C.; Grobusch, M.P. Biological warfare, bioterrorism, and biocrime. Clin. Microbiol. Infect., 2014, 20(6), 488-496.
[http://dx.doi.org/10.1111/1469-0691.12699] [PMID: 24890710]
[25]
Eitzen, E.M., Jr; Takafuji, E.T. Historical overview of biological warfare. In: Medical aspects of chemical and biologial warfare; , 1997; pp. 415-423.
[26]
Musshoff, F.; Madea, B. Ricin poisoning and forensic toxicology. Drug Test. Anal., 2009, 1(4), 184-191.
[http://dx.doi.org/10.1002/dta.27] [PMID: 20355196]
[27]
Sphyris, N.; Lord, J.M.; Wales, R.; Roberts, L.M. Mutational analysis of the Ricinus lectin B-chains. Galactose-binding ability of the 2 γ subdomain of Ricinus communis agglutinin B-chain. J. Biol. Chem., 1995, 270(35), 20292-20297.
[http://dx.doi.org/10.1074/jbc.270.35.20292] [PMID: 7657599]
[28]
Spooner, R.A.; Smith, D.C.; Easton, A.J.; Roberts, L.M.; Lord, M.J. Retrograde transport pathways utilised by viruses and protein toxins. Virol. J., 2006, 3(1), 26.
[http://dx.doi.org/10.1186/1743-422X-3-26] [PMID: 16603059]
[29]
Bassik, M.C.; Kampmann, M.; Lebbink, R.J.; Wang, S.; Hein, M.Y.; Poser, I.; Weibezahn, J.; Horlbeck, M.A.; Chen, S.; Mann, M.; Hyman, A.A.; LeProust, E.M.; McManus, M.T.; Weissman, J.S. A systematic mammalian genetic interaction map reveals pathways underlying ricin susceptibility. Cell, 2013, 152(4), 909-922.
[http://dx.doi.org/10.1016/j.cell.2013.01.030] [PMID: 23394947]
[30]
Tian, S.; Muneeruddin, K.; Choi, M.Y.; Tao, L.; Bhuiyan, R.H.; Ohmi, Y.; Furukawa, K.; Furukawa, K.; Boland, S.; Shaffer, S.A.; Adam, R.M.; Dong, M. Genome-wide CRISPR screens for Shiga toxins and ricin reveal Golgi proteins critical for glycosylation. PLoS Biol., 2018, 16(11), e2006951.
[http://dx.doi.org/10.1371/journal.pbio.2006951] [PMID: 30481169]
[31]
Wu, Y.; Taisne, C.; Mahtal, N.; Forrester, A.; Lussignol, M.; Cintrat, J.C.; Esclatine, A.; Gillet, D.; Barbier, J. Autophagic degradation is involved in cell protection against ricin toxin. Toxins (Basel), 2023, 15(5), 304.
[http://dx.doi.org/10.3390/toxins15050304] [PMID: 37235339]
[32]
Spooner, R.A.; Watson, P.D.; Marsden, C.J.; Smith, D.C.; Moore, K.A.H.; Cook, J.P.; Lord, J.M.; Roberts, L.M. Protein disulphide-isomerase reduces ricin to its A and B chains in the endoplasmic reticulum. Biochem. J., 2004, 383(2), 285-293.
[http://dx.doi.org/10.1042/BJ20040742]
[33]
Bellisola, G.; Fracasso, G.; Ippoliti, R.; Menestrina, G.; Rosén, A.; Soldà, S.; Udali, S.; Tomazzolli, R.; Tridente, G.; Colombatti, M. Reductive activation of ricin and ricin A-chain immunotoxins by protein disulfide isomerase and thioredoxin reductase. Biochem. Pharmacol., 2004, 67(9), 1721-1731.
[http://dx.doi.org/10.1016/j.bcp.2004.01.013] [PMID: 15081871]
[34]
Endo, Y.; Tsurugi, K. The RNA N-glycosidase activity of ricin A-chain. The characteristics of the enzymatic activity of ricin A-chain with ribosomes and with rRNA. J. Biol. Chem., 1988, 263(18), 8735-8739.
[http://dx.doi.org/10.1016/S0021-9258(18)68367-X] [PMID: 3288622]
[35]
Lord, J.M.; Roberts, L.M.; Robertus, J.D. Ricin: Structure, mode of action, and some current applications. FASEB J., 1994, 8(2), 201-208.
[http://dx.doi.org/10.1096/fasebj.8.2.8119491] [PMID: 8119491]
[36]
Olsnes, S. The history of ricin, abrin and related toxins. Toxicon, 2004, 44(4), 361-370.
[http://dx.doi.org/10.1016/j.toxicon.2004.05.003] [PMID: 15302520]
[37]
Olsnes, S.; Fernandez-Puentes, C.; Carrasco, L.; Vazquez, D. Ribosome inactivation by the toxic lectins abrin and ricin. Kinetics of the enzymic activity of the toxin A-chains. Eur. J. Biochem., 1975, 60(1), 281-288.
[http://dx.doi.org/10.1111/j.1432-1033.1975.tb21001.x] [PMID: 1204642]
[38]
Olson, M.A.; Carra, J.H.; Roxas-Duncan, V.; Wannemacher, R.W.; Smith, L.A.; Millard, C.B. Finding a new vaccine in the ricin protein fold. Protein Eng. Des. Sel., 2004, 17(4), 391-397.
[http://dx.doi.org/10.1093/protein/gzh043] [PMID: 15187223]
[39]
Deeks, E.D.; Cook, J.P.; Day, P.J.; Smith, D.C.; Roberts, L.M.; Lord, J.M. The low lysine content of ricin A chain reduces the risk of proteolytic degradation after translocation from the endoplasmic reticulum to the cytosol. Biochemistry, 2002, 41(10), 3405-3413.
[http://dx.doi.org/10.1021/bi011580v] [PMID: 11876649]
[40]
Perkel, J.M. The software that powers scientific illustration. Nature, 2020, 582(7810), 137-138.
[http://dx.doi.org/10.1038/d41586-020-01404-7] [PMID: 32385367]
[41]
Franke, H.; Scholl, R.; Aigner, A. Ricin and Ricinus communis in pharmacology and toxicology-from ancient use and “Papyrus Ebers” to modern perspectives and “poisonous plant of the year 2018”. Naunyn Schmiedebergs Arch. Pharmacol., 2019, 392(10), 1181-1208.
[http://dx.doi.org/10.1007/s00210-019-01691-6] [PMID: 31359089]
[42]
Ho, M.C.; Sturm, M.B.; Almo, S.C.; Schramm, V.L. Transition state analogues in structures of ricin and saporin ribosome-inactivating proteins. Proc. Natl. Acad. Sci., 2009, 106(48), 20276-20281.
[http://dx.doi.org/10.1073/pnas.0911606106] [PMID: 19920175]
[43]
Pincus, S.H.; Smallshaw, J.E.; Song, K.; Berry, J.; Vitetta, E.S. Passive and active vaccination strategies to prevent ricin poisoning. Toxins, 2011, 3(9), 1163-1184.
[http://dx.doi.org/10.3390/toxins3091163] [PMID: 22069761]
[44]
Brey, R.N., III; Mantis, N.J.; Pincus, S.H.; Vitetta, E.S.; Smith, L.A.; Roy, C.J. Recent advances in the development of vaccines against ricin. Hum. Vaccin. Immunother., 2016, 12(5), 1196-1201.
[http://dx.doi.org/10.1080/21645515.2015.1124202] [PMID: 26810367]
[45]
Maddaloni, M.; Cooke, C.; Wilkinson, R.; Stout, A.V.; Eng, L.; Pincus, S.H. Immunological characteristics associated with the protective efficacy of antibodies to ricin. J. Immunol., 2004, 172(10), 6221-6228.
[http://dx.doi.org/10.4049/jimmunol.172.10.6221] [PMID: 15128810]
[46]
Smallshaw, J.; Firan, A.; Fulmer, J.R.; Ruback, S.L.; Ghetie, V.; Vitetta, E.S. A novel recombinant vaccine which protects mice against ricin intoxication. Vaccine, 2002, 20(27-28), 3422-3427.
[http://dx.doi.org/10.1016/S0264-410X(02)00312-2] [PMID: 12213413]
[47]
Smallshaw, J.E.; Vitetta, E.S. Ricin vaccine development; Ricin and Shiga Toxins, 2011, pp. 259-272.
[48]
Carra, J.H.; Wannemacher, R.W.; Tammariello, R.F.; Lindsey, C.Y.; Dinterman, R.E.; Schokman, R.D.; Smith, L.A. Improved formulation of a recombinant ricin A-chain vaccine increases its stability and effective antigenicity. Vaccine, 2007, 25(21), 4149-4158.
[http://dx.doi.org/10.1016/j.vaccine.2007.03.011] [PMID: 17408819]
[49]
McLain, D.E.; Lewis, B.S.; Chapman, J.L.; Wannemacher, R.W.; Lindsey, C.Y.; Smith, L.A. Protective effect of two recombinant ricin subunit vaccines in the New Zealand white rabbit subjected to a lethal aerosolized ricin challenge: Survival, immunological response, and histopathological findings. Toxicol. Sci., 2012, 126(1), 72-83.
[http://dx.doi.org/10.1093/toxsci/kfr274] [PMID: 21987460]
[50]
Smallshaw, J.E.; Richardson, J.A.; Pincus, S.; Schindler, J.; Vitetta, E.S. Preclinical toxicity and efficacy testing of RiVax, a recombinant protein vaccine against ricin. Vaccine, 2005, 23(39), 4775-4784.
[http://dx.doi.org/10.1016/j.vaccine.2005.04.037] [PMID: 15961194]
[51]
Smallshaw, J.E.; Ghetie, V.; Rizo, J.; Fulmer, J.R.; Trahan, L.L.; Ghetie, M.A.; Vitetta, E.S. Genetic engineering of an immunotoxin to eliminate pulmonary vascular leak in mice. Nat. Biotechnol., 2003, 21(4), 387-391.
[http://dx.doi.org/10.1038/nbt800] [PMID: 12627168]
[52]
Smallshaw, J.E.; Richardson, J.A.; Vitetta, E.S. RiVax, a recombinant ricin subunit vaccine, protects mice against ricin delivered by gavage or aerosol. Vaccine, 2007, 25(42), 7459-7469.
[http://dx.doi.org/10.1016/j.vaccine.2007.08.018] [PMID: 17875350]
[53]
Vitetta, E.S.; Smallshaw, J.E.; Coleman, E.; Jafri, H.; Foster, C.; Munford, R.; Schindler, J. A pilot clinical trial of a recombinant ricin vaccine in normal humans. Proc. Natl. Acad. Sci., 2006, 103(7), 2268-2273.
[http://dx.doi.org/10.1073/pnas.0510893103] [PMID: 16461456]
[54]
Roy, C.J.; Ehrbar, D.; Van Slyke, G.; Doering, J.; Didier, P.J.; Doyle-Meyers, L.; Donini, O.; Vitetta, E.S.; Mantis, N.J. Serum antibody profiling identifies vaccine-induced correlates of protection against aerosolized ricin toxin in rhesus macaques. NPJ Vaccines, 2022, 7(1), 164.
[http://dx.doi.org/10.1038/s41541-022-00582-x] [PMID: 36526642]
[55]
McLain, D.E.; Horn, T.L.; Detrisac, C.J.; Lindsey, C.Y.; Smith, L.A. Progress in biological threat agent vaccine development: A repeat-dose toxicity study of a recombinant ricin toxin A-chain (rRTA) 1-33/44-198 vaccine (RVEc) in male and female New Zealand white rabbits. Int. J. Toxicol., 2011, 30(2), 143-152.
[http://dx.doi.org/10.1177/1091581810396730] [PMID: 21378370]
[56]
Porter, A.; Phillips, G.; Smith, L.; Erwin-Cohen, R.; Tammariello, R.; Hale, M.; DaSilva, L. Evaluation of a ricin vaccine candidate (RVEc) for human toxicity using an in vitro vascular leak assay. Toxicon, 2011, 58(1), 68-75.
[http://dx.doi.org/10.1016/j.toxicon.2011.05.005] [PMID: 21616091]
[57]
O’Hara, J.M.; Brey, R.N., III; Mantis, N.J. Comparative efficacy of two leading candidate ricin toxin a subunit vaccines in mice. Clin. Vaccine Immunol., 2013, 20(6), 789-794.
[http://dx.doi.org/10.1128/CVI.00098-13] [PMID: 23515013]
[58]
Pittman, P.R.; Reisler, R.B.; Lindsey, C.Y.; Güereña, F.; Rivard, R.; Clizbe, D.P.; Chambers, M.; Norris, S.; Smith, L.A. Safety and immunogenicity of ricin vaccine, RVEc™, in a Phase 1 clinical trial. Vaccine, 2015, 33(51), 7299-7306.
[http://dx.doi.org/10.1016/j.vaccine.2015.10.094] [PMID: 26546259]
[59]
Rasetti-Escargueil, C.; Avril, A. Medical countermeasures against ricin intoxication. Toxins, 2023, 15(2), 100.
[http://dx.doi.org/10.3390/toxins15020100] [PMID: 36828415]
[60]
Rocha-Santos, A.; Chaves, E.J.F.; Grillo, I.B.; de Freitas, A.S.; Araújo, D.A.M.; Rocha, G.B. Thermochemical and quantum descriptor calculations for gaining insight into ricin toxin A (RTA) Inhibitors. ACS Omega, 2021, 6(13), 8764-8777.
[http://dx.doi.org/10.1021/acsomega.0c02588] [PMID: 33842748]
[61]
Chaves, E.J.F.; Gomes da Cruz, L.E.; Padilha, I.Q.M.; Silveira, C.H.; Araujo, D.A.M.; Rocha, G.B. Discovery of RTA ricin subunit inhibitors: A computational study using PM7 quantum chemical method and steered molecular dynamics. J. Biomol. Struct. Dyn., 2022, 40(12), 5427-5445.
[http://dx.doi.org/10.1080/07391102.2021.1878058] [PMID: 33526002]
[62]
Botelho, F.D.; dos Santos, M.C.; Gonçalves, A.S.; Kuca, K.; Valis, M.; LaPlante, S.R.; França, T.C.C.; de Almeida, J.S.F.D. Ligand-based virtual screening, molecular docking, molecular dynamics, and mm-pbsa calculations towards the identification of potential novel ricin inhibitors. Toxins, 2020, 12(12), 746.
[http://dx.doi.org/10.3390/toxins12120746] [PMID: 33256167]
[63]
Botelho, F.D.; Santos, M.C.; Gonçalves, A.S.; França, T.C.; LaPlante, S.R.; de Almeida, J.S. Identification of novel potential ricin inhibitors by virtual screening, molecular docking, molecular dynamics and MM-PBSA calculations: A drug repurposing approach. J. Biomol. Struct. Dyn., 2020, 1-11.
[PMID: 33410376]
[64]
Jasheway, K.; Pruet, J.; Anslyn, E.V.; Robertus, J.D. Structure-based design of ricin inhibitors. Toxins, 2011, 3(10), 1233-1248.
[http://dx.doi.org/10.3390/toxins3101233] [PMID: 22069693]
[65]
Pruet, J.M.; Saito, R.; Manzano, L.A.; Jasheway, K.R.; Wiget, P.A.; Kamat, I.; Anslyn, E.V.; Robertus, J.D. Optimized 5-membered heterocycle-linked pterins for the inhibition of Ricin Toxin A. ACS Med. Chem. Lett., 2012, 3(7), 588-591.
[http://dx.doi.org/10.1021/ml300099t] [PMID: 23050058]
[66]
França, T.C.C.; Botelho, F.D.; Drummond, M.L.; LaPlante, S.R. Theoretical investigation of repurposed drugs potentially capable of binding to the catalytic site and the secondary binding pocket of subunit a of ricin. ACS Omega, 2022, 7(36), 32805-32815.
[http://dx.doi.org/10.1021/acsomega.2c04819] [PMID: 36120038]
[67]
Pruet, J.M.; Jasheway, K.R.; Manzano, L.A.; Bai, Y.; Anslyn, E.V.; Robertus, J.D. 7-Substituted pterins provide a new direction for ricin A chain inhibitors. Eur. J. Med. Chem., 2011, 46(9), 3608-3615.
[http://dx.doi.org/10.1016/j.ejmech.2011.05.025] [PMID: 21641093]
[68]
Saito, R.; Pruet, J.M.; Manzano, L.A.; Jasheway, K.; Monzingo, A.F.; Wiget, P.A.; Kamat, I.; Anslyn, E.V.; Robertus, J.D. Peptide-conjugated pterins as inhibitors of ricin toxin A. J. Med. Chem., 2013, 56(1), 320-329.
[http://dx.doi.org/10.1021/jm3016393] [PMID: 23214944]
[69]
Wiget, P.A.; Manzano, L.A.; Pruet, J.M.; Gao, G.; Saito, R.; Monzingo, A.F.; Jasheway, K.R.; Robertus, J.D.; Anslyn, E.V. Sulfur incorporation generally improves Ricin inhibition in pterin-appended glycine-phenylalanine dipeptide mimics. Bioorg. Med. Chem. Lett., 2013, 23(24), 6799-6804.
[http://dx.doi.org/10.1016/j.bmcl.2013.10.017] [PMID: 24432385]
[70]
Monzingo, A.F.; Robertus, J.D. X-ray analysis of substrate analogs in the ricin A-chain active site. J. Mol. Biol., 1992, 227(4), 1136-1145.
[http://dx.doi.org/10.1016/0022-2836(92)90526-P] [PMID: 1433290]
[71]
Yan, X.; Hollis, T.; Svinth, M.; Day, P.; Monzingo, A.F.; Milne, G.W.A.; Robertus, J.D. Structure-based identification of a ricin inhibitor. J. Mol. Biol., 1997, 266(5), 1043-1049.
[http://dx.doi.org/10.1006/jmbi.1996.0865] [PMID: 9086280]
[72]
Bai, Y.; Monzingo, A.F.; Robertus, J.D. The X-ray structure of ricin A chain with a novel inhibitor. Arch. Biochem. Biophys., 2009, 483(1), 23-28.
[http://dx.doi.org/10.1016/j.abb.2008.12.013] [PMID: 19138659]
[73]
Zhao, X.; Li, H.; Li, J.; Liu, K.; Wang, B.; Wang, Y.; Li, X.; Zhong, W. Novel small molecule retrograde transport blocker confers post-exposure protection against ricin intoxication. Acta Pharm. Sin. B, 2020, 10(3), 498-511.
[http://dx.doi.org/10.1016/j.apsb.2019.08.005] [PMID: 32140395]
[74]
Seaman, M.N.J.; Peden, A.A. Ricin toxin hits a retrograde roadblock. Cell, 2010, 141(2), 222-224.
[http://dx.doi.org/10.1016/j.cell.2010.03.044] [PMID: 20403318]
[75]
Park, J.G.; Kahn, J.N.; Tumer, N.E.; Pang, Y.P. Chemical structure of Retro-2, a compound that protects cells against ribosome-inactivating proteins. Sci. Rep., 2012, 2(1), 631.
[http://dx.doi.org/10.1038/srep00631] [PMID: 22953052]
[76]
Li, X.P.; Harijan, R.K.; Cao, B.; Kahn, J.N.; Pierce, M.; Tsymbal, A.M.; Roberge, J.Y.; Augeri, D.; Tumer, N.E. Synthesis and structural characterization of ricin inhibitors targeting ribosome binding using fragment-based methods and structure-based design. J. Med. Chem., 2021, 64(20), 15334-15348.
[http://dx.doi.org/10.1021/acs.jmedchem.1c01370] [PMID: 34648707]
[77]
Li, X.P.; Harijan, R.K.; Kahn, J.N.; Schramm, V.L.; Tumer, N.E. Small molecule inhibitors targeting the interaction of ricin toxin A subunit with ribosomes. ACS Infect. Dis., 2020, 6(7), 1894-1905.
[http://dx.doi.org/10.1021/acsinfecdis.0c00127] [PMID: 32428396]
[78]
Bai, Y.; Watt, B.; Wahome, P.G.; Mantis, N.J.; Robertus, J.D. Identification of new classes of ricin toxin inhibitors by virtual screening. Toxicon, 2010, 56(4), 526-534.
[http://dx.doi.org/10.1016/j.toxicon.2010.05.009] [PMID: 20493201]
[79]
Abagyan, R.; Totrov, M.; Kuznetsov, D. ICM—A new method for protein modeling and design: Applications to docking and structure prediction from the distorted native conformation. J. Comput. Chem., 1994, 15(5), 488-506.
[http://dx.doi.org/10.1002/jcc.540150503]
[80]
Jones, G.; Willett, P.; Glen, R.C.; Leach, A.R.; Taylor, R. Development and validation of a genetic algorithm for flexible docking 1 1Edited by F. E. Cohen. J. Mol. Biol., 1997, 267(3), 727-748.
[http://dx.doi.org/10.1006/jmbi.1996.0897] [PMID: 9126849]
[81]
Mishra, V.; Siva Prasad, C.V.S. Ligand based virtual screening to find novel inhibitors against plant toxin Ricin by using the ZINC database. Bioinformation, 2011, 7(1), 46-51.
[http://dx.doi.org/10.6026/97320630007046] [PMID: 21938204]
[82]
Korb, O.; Stützle, T.; Exner, T.E. Empirical scoring functions for advanced protein-ligand docking with PLANTS. J. Chem. Inf. Model., 2009, 49(1), 84-96.
[http://dx.doi.org/10.1021/ci800298z] [PMID: 19125657]
[83]
Boittier, E.D.; Tang, Y.Y.; Buckley, M.E.; Schuurs, Z.P.; Richard, D.J.; Gandhi, N.S. Assessing molecular docking tools to guide targeted drug discovery of CD38 inhibitors. Int. J. Mol. Sci., 2020, 21(15), 5183.
[http://dx.doi.org/10.3390/ijms21155183] [PMID: 32707824]
[84]
Pagadala, N.S.; Syed, K.; Tuszynski, J. Software for molecular docking: A review. 2017, 9(2), 91-102.
[http://dx.doi.org/10.1007/s12551-016-0247-1]
[85]
Abraham, M.J.; Murtola, T.; Schulz, R.; Páll, S.; Smith, J.C.; Hess, B.; Lindahl, E. GROMACS: High performance molecular simulations through multi-level parallelism from laptops to supercomputers. SoftwareX, 2015, 1-2, 19-25.
[http://dx.doi.org/10.1016/j.softx.2015.06.001]
[86]
Nelson, M.T.; Humphrey, W.; Gursoy, A.; Dalke, A.; Kalé, L.V.; Skeel, R.D.; Schulten, K. NAMD: A parallel, object-oriented molecular dynamics program. Int. J. High Perform. Comput. Appl., 1996, 10(4), 251-268.
[http://dx.doi.org/10.1177/109434209601000401]
[87]
Phillips, J.C.; Hardy, D.J.; Maia, J.D.C.; Stone, J.E.; Ribeiro, J.V.; Bernardi, R.C.; Buch, R.; Fiorin, G.; Hénin, J.; Jiang, W.; McGreevy, R.; Melo, M.C.R.; Radak, B.K.; Skeel, R.D.; Singharoy, A.; Wang, Y.; Roux, B.; Aksimentiev, A.; Luthey-Schulten, Z.; Kalé, L.V.; Schulten, K.; Chipot, C.; Tajkhorshid, E. Scalable molecular dynamics on CPU and GPU architectures with NAMD. J. Chem. Phys., 2020, 153(4), 044130.
[http://dx.doi.org/10.1063/5.0014475] [PMID: 32752662]
[88]
Godal, A.; Fodstad, Ø.; Pihl, A. Antibody formation against the cytotoxic proteins abrin and ricin in humans and mice. Int. J. Cancer, 1983, 32(4), 515-521.
[http://dx.doi.org/10.1002/ijc.2910320420] [PMID: 6618711]
[89]
Houston, L.L. Protection of mice from ricin poisoning by treatment with antibodies directed against ricin. J. Toxicol. Clin. Toxicol., 1982, 19(4), 385-389.
[http://dx.doi.org/10.3109/15563658208992492] [PMID: 7143524]
[90]
Pelat, T.; Hust, M.; Hale, M.; Lefranc, M.P.; Dübel, S.; Thullier, P. Isolation of a human-like antibody fragment (scFv) that neutralizes ricin biological activity. BMC Biotechnol., 2009, 9(1), 60.
[http://dx.doi.org/10.1186/1472-6750-9-60] [PMID: 19563687]
[91]
Wang, Y.; Guo, L.; Zhao, K.; Chen, J.; Feng, J.; Sun, Y.; Li, Y.; Shen, B. Novel chimeric anti-ricin antibody C4C13 with neutralizing activity against ricin toxicity. Biotechnol. Lett., 2007, 29(12), 1811-1816.
[http://dx.doi.org/10.1007/s10529-007-9478-3] [PMID: 17657413]
[92]
Pratt, T.S.; Pincus, S.H.; Hale, M.L.; Moreira, A.L.; Roy, C.J.; Tchou-Wong, K.M. Oropharyngeal aspiration of ricin as a lung challenge model for evaluation of the therapeutic index of antibodies against ricin A-chain for post-exposure treatment. Exp. Lung Res., 2007, 33(8-9), 459-481.
[http://dx.doi.org/10.1080/01902140701731805] [PMID: 17994372]
[93]
Vance, D.J.; Tremblay, J.M.; Mantis, N.J.; Shoemaker, C.B. Stepwise engineering of heterodimeric single domain camelid VHH antibodies that passively protect mice from ricin toxin. J. Biol. Chem., 2013, 288(51), 36538-36547.
[http://dx.doi.org/10.1074/jbc.M113.519207] [PMID: 24202178]
[94]
Poli, M.A.; Rivera, V.R.; Pitt, M.L.; Vogel, P. Aerosolized specific antibody protects mice from lung injury associated with aerosolized ricin exposure. Toxicon, 1996, 34(9), 1037-1044.
[http://dx.doi.org/10.1016/0041-0101(96)00047-5] [PMID: 8896195]
[95]
Foxwell, B.; Detre, S.; Donovan, T.; Thorpe, P. The use of anti-ricin antibodies to protect mice intoxicated with ricin. Toxicology, 1985, 34(1), 79-88.
[http://dx.doi.org/10.1016/0300-483X(85)90080-0] [PMID: 3969682]
[96]
McGuinness, C.R.; Mantis, N.J. Characterization of a novel high-affinity monoclonal immunoglobulin G antibody against the ricin B subunit. Infect. Immun., 2006, 74(6), 3463-3470.
[http://dx.doi.org/10.1128/IAI.00324-06] [PMID: 16714577]
[97]
Vance, D.J.; Poon, A.Y.; Mantis, N.J. Sites of vulnerability on ricin B chain revealed through epitope mapping of toxin-neutralizing monoclonal antibodies. PLoS One, 2020, 15(11), e0236538.
[http://dx.doi.org/10.1371/journal.pone.0236538] [PMID: 33166282]
[98]
Yermakova, A.; Mantis, N.J. Protective immunity to ricin toxin conferred by antibodies against the toxin’s binding subunit (RTB). Vaccine, 2011, 29(45), 7925-7935.
[http://dx.doi.org/10.1016/j.vaccine.2011.08.075] [PMID: 21872634]
[99]
Hu, W.G.; Yin, J.; Chau, D.; Hu, C.C.; Lillico, D.; Yu, J.; Negrych, L.M.; Cherwonogrodzky, J.W. Conformation-dependent high-affinity potent ricin-neutralizing monoclonal antibodies. Biomed. Res. Int., 2013, 2013, 471346.
[http://dx.doi.org/10.1155/2013/471346]
[100]
Prigent, J.; Panigai, L.; Lamourette, P.; Sauvaire, D.; Devilliers, K.; Plaisance, M.; Volland, H.; Créminon, C.; Simon, S. Neutralising antibodies against ricin toxin. PLoS One, 2011, 6(5), e20166.
[http://dx.doi.org/10.1371/journal.pone.0020166] [PMID: 21633505]
[101]
Orsini Delgado, M.L.; Avril, A.; Prigent, J.; Dano, J.; Rouaix, A.; Worbs, S.; Dorner, B.G.; Rougeaux, C.; Becher, F.; Fenaille, F.; Livet, S.; Volland, H.; Tournier, J.N.; Simon, S. Ricin antibodies’ neutralizing capacity against different ricin isoforms and cultivars. Toxins, 2021, 13(2), 100.
[http://dx.doi.org/10.3390/toxins13020100] [PMID: 33573016]
[102]
Rong, Y.; Torres-Velez, F.J.; Ehrbar, D.; Doering, J.; Song, R.; Mantis, N.J. An intranasally administered monoclonal antibody cocktail abrogates ricin toxin-induced pulmonary tissue damage and inflammation. Hum. Vaccin. Immunother., 2020, 16(4), 793-807.
[http://dx.doi.org/10.1080/21645515.2019.1664243] [PMID: 31589555]
[103]
Rong, Y.; Pauly, M.; Guthals, A.; Pham, H.; Ehrbar, D.; Zeitlin, L.; Mantis, N.J. A humanized monoclonal antibody cocktail to prevent pulmonary ricin intoxication. Toxins, 2020, 12(4), 215.
[http://dx.doi.org/10.3390/toxins12040215] [PMID: 32235318]
[104]
Yu, H.; Li, S.; Xu, N.; Liu, W. Ricin toxin and its neutralizing antibodies: A review. Toxicon, 2022, 214, 47-53.
[http://dx.doi.org/10.1016/j.toxicon.2022.05.005] [PMID: 35595086]

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