Identification of agents effective against multiple toxins and viruses by host-oriented cell targeting.
Sci Rep
; 5: 13476, 2015 Aug 27.
Article
em En
| MEDLINE
| ID: mdl-26310922
ABSTRACT
A longstanding and still-increasing threat to the effective treatment of infectious diseases is resistance to antimicrobial countermeasures. Potentially, the targeting of host proteins and pathways essential for the detrimental effects of pathogens offers an approach that may discover broad-spectrum anti-pathogen countermeasures and circumvent the effects of pathogen mutations leading to resistance. Here we report implementation of a strategy for discovering broad-spectrum host-oriented therapies against multiple pathogenic agents by multiplex screening of drugs for protection against the detrimental effects of multiple pathogens, identification of host cell pathways inhibited by the drug, and screening for effects of the agent on other pathogens exploiting the same pathway. We show that a clinically used antimalarial drug, Amodiaquine, discovered by this strategy, protects host cells against infection by multiple toxins and viruses by inhibiting host cathepsin B. Our results reveal the practicality of discovering broadly acting anti-pathogen countermeasures that target host proteins exploited by pathogens.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Toxinas Bacterianas
/
Vírus
/
Interações Hospedeiro-Patógeno
/
Antígenos de Bactérias
Tipo de estudo:
Diagnostic_studies
Limite:
Animals
/
Humans
País/Região como assunto:
America do norte
Idioma:
En
Revista:
Sci Rep
Ano de publicação:
2015
Tipo de documento:
Article