Bithionol blocks pathogenicity of bacterial toxins, ricin, and Zika virus.
Bithionol blocks pathogenicity of bacterial toxins, ricin, and Zika virus.
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DOI：
10.1038/srep34475
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发表时间：
2016-09-30
影响因子：
4.6
通讯作者：
Martchenko M
中科院分区：
文献类型：
--
作者：
Leonardi W;Zilbermintz L;Cheng LW;Zozaya J;Tran SH;Elliott JH;Polukhina K;Manasherob R;Li A;Chi X;Gharaibeh D;Kenny T;Zamani R;Soloveva V;Haddow AD;Nasar F;Bavari S;Bassik MC;Cohen SN;Levitin A;Martchenko M
Diverse pathogenic agents often utilize overlapping host networks, and hub proteins within these networks represent attractive targets for broad-spectrum drugs. Using bacterial toxins, we describe a new approach for discovering broad-spectrum therapies capable of inhibiting host proteins that mediate multiple pathogenic pathways. This approach can be widely used, as it combines genetic-based target identification with cell survival-based and protein function-based multiplex drug screens, and concurrently discovers therapeutic compounds and their protein targets. Using B-lymphoblastoid cells derived from the HapMap Project cohort of persons of African, European, and Asian ancestry we identified host caspases as hub proteins that mediate the lethality of multiple pathogenic agents. We discovered that an approved drug, Bithionol, inhibits host caspases and also reduces the detrimental effects of anthrax lethal toxin, diphtheria toxin, cholera toxin, Pseudomonas aeruginosa exotoxin A, Botulinum neurotoxin, ricin, and Zika virus. Our study reveals the practicality of identifying host proteins that mediate multiple disease pathways and discovering broad-spectrum therapies that target these hub proteins.
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影响因子：
--
作者：
Boldt, Grant E.;Kennedy, Jack P.;Janda, Kim D.
通讯作者：
Janda, Kim D.
影响因子：
6.1
作者：
Eleuteri, Simona;Di Giovanni, Saviana;Rockenstein, Edward;Mante, Mike;Adame, Antony;Trejo, Margarita;Wrasidlo, Wolf;Wu, Fang;Fraering, Patrick C.;Masliah, Eliezer;Lashuel, Hilal A.
通讯作者：
Lashuel, Hilal A.
DOI：
10.1038/nri3131
发表时间：
2011-12-23
期刊：
Nature reviews. Immunology
影响因子：
--
作者：
Mocarski ES;Upton JW;Kaiser WJ
通讯作者：
Kaiser WJ
影响因子：
2.7
作者：
Komatsu, N;Oda, T;Muramatsu, T
通讯作者：
Muramatsu, T
影响因子：
4.8
作者：
Ha, Soon-Duck;Ham, Boram;Kim, Sung Ouk
通讯作者：
Kim, Sung Ouk