Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 60, Issue 4, Pages 1400-1416Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jmedchem.6b01521
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Funding
- Chiesi Foundation
- University of Parma
- Italian Cancer Research Association (AIRC) [IG15868]
- Cystic Fibrosis Trust (CFT) [RS31]
- China Scholarship Council (CSC) [201403250056]
- European Union as a Marie-Sklodowska Curie European Training Network ANTIVIRALS [GA 642434]
- Cystic Fibrosis Trust [RS31] Funding Source: researchfish
- Medical Research Council [1702423] Funding Source: researchfish
- Sparks Charity [15UCL04] Funding Source: researchfish
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Enteroviruses (EVs) are among the most frequent infectious agents in humans worldwide and represent the leading cause of upper respiratory tract infections. No drugs for the treatment of EV infections are currently available. Recent studies have also linked EV infection with pulmonary exacerbations, especially in cystic fibrosis (CF) patients, and the importance of this link is probably underestimated. The aim of this work was to develop a new class of multitarget agents active both as broad-spectrum antivirals and as correctors of the F508del-cystic fibrosis transmembrane conductance regulator (CFTR) folding defect responsible for >90% of CF cases. We report herein the discovery of the first small molecules able to simultaneously act as correctors of the F508del-CFTR folding defect and as broad-spectrum antivirals against a panel of EVs representative of all major species.
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