U.S. flag

An official website of the United States government

Dot gov

Official websites use .gov
A .gov website belongs to an official government organization in the United States.

Https

Secure .gov websites use HTTPS
A lock ( ) or https:// means you’ve safely connected to the .gov website. Share sensitive information only on official, secure websites.

PubAg

Main content area

Bithionol blocks pathogenicity of bacterial toxins, ricin, and Zika virus

Author:
William Leonardi, Leeor Zilbermintz, Luisa W. W. Cheng, Josue Zozaya, Sharon H. Tran, Jeffrey H. Elliott, Kseniya Polukhina, Robert Manasherob, Amy Li, Xiaoli Chi, Dima Gharaibeh, Tara Kenny, Rouzbeh Zamani, Veronica Soloveva, Andrew D. Haddow, Farooq Nasar, Sina Bavari, Michael C. Bassik, Stanley N. Cohen, Anastasia Levitin, Mikhail Martchenko
Source:
Scientific Reports 2016 v.6 no.1 pp. -
ISSN:
2045-2322
Subject:
Africans, Asians, Europeans, Pseudomonas aeruginosa, Zika virus, ancestry, anthrax, anti-infective agents, botulinum toxin, caspases, cholera toxin, drugs, enzyme inhibitors, exotoxins, hosts, pathogenicity, ricin, therapeutics
Abstract:
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.
Agid:
5678135
Handle:
10113/5678135