2026-06-19T16:57:27Zhttps://riubu.ubu.es/oai/request

oai:riubu.ubu.es:10259/79982023-11-23T12:25:51Zcom_10259_4862com_10259_5086com_10259_2604col_10259_4863

Martínez Gil, Luis Ayllón Barasoain, Juan Ortigoza, Mila Brum García Sastre, Adolfo Shaw, Megan L. Palese, Peter 2023-11-13T08:06:51Z 2023-11-13T08:06:51Z 2012 http://hdl.handle.net/10259/7998 10.1371/journal.pone.0049049 1932-6203 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. 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. application/pdf eng Public Library of Science PLoS ONE. 2012, V. 7, n. 11, e49049 https://doi.org/10.1371/journal.pone.0049049 Atribución 4.0 Internacional http://creativecommons.org/licenses/by/4.0/ info:eu-repo/semantics/openAccess Medicina Salud Microbiología Enfermedades infecciosas Medicine Health Microbiology Communicable diseases Identification of Small Molecules with Type I Interferon Inducing Properties by High-Throughput Screening info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion PLoS ONE 7 11 e49049