RT info:eu-repo/semantics/article
T1 Identification of Small Molecules with Type I Interferon Inducing Properties by High-Throughput Screening
A1 Martínez Gil, Luis
A1 Ayllón Barasoain, Juan
A1 Ortigoza, Mila Brum
A1 García Sastre, Adolfo
A1 Shaw, Megan L.
A1 Palese, Peter
K1 Medicina
K1 Medicine
K1 Salud
K1 Health
K1 Microbiología
K1 Microbiology
K1 Enfermedades infecciosas
K1 Communicable diseases
AB The continuous emergence of virus that are resistant to current anti-viral drugs, combined with the introduction of new viral pathogens for which no therapeutics are available, creates an urgent need for the development of novel broad spectrum antivirals. Type I interferon (IFN) can, by modulating the cellular expression profile, stimulate a non-specific antiviral state. The antiviral and adjuvant properties of IFN have been extensively demonstrated; however, its clinical application has been so far limited. We have developed a human cell-based assay that monitors IFN-β production for use in a high throughput screen. Using this assay we screened 94,398 small molecules and identified 18 compounds with IFN-inducing properties. Among these, 3 small molecules (C3, E51 and L56) showed activity not only in human but also in murine and canine derived cells. We further characterized C3 and showed that this molecule is capable of stimulating an anti-viral state in human-derived lung epithelial cells. Furthermore, the IFN-induction by C3 is not diminished by the presence of influenza A virus NS1 protein or hepatitis C virus NS3/4A protease, which make this molecule an interesting candidate for the development of a new type of broad-spectrum antiviral. In addition, the IFN-inducing properties of C3 also suggest its potential use as vaccine adjuvant.
PB Public Library of Science
YR 2012
FD 2012
LK http://hdl.handle.net/10259/7998
UL http://hdl.handle.net/10259/7998
LA eng
NO This work was supported in part by National Institutes of Health grants: HHSN272200900032C and U54308 AI057159. No additional external funding received for this study. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
DS Repositorio Institucional de la Universidad de Burgos
RD 10-may-2024