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Nat Rev Drug Discov. 2018 Jan;17(1):35-56. doi: 10.1038/nrd.2017.162. Epub 2017 Sep 22.

Host-directed therapies for bacterial and viral infections.

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Department of Immunology, Max Planck Institute for Infection Biology, Charit├ęplatz 1, 10117 Berlin, Germany.
Institute of Immunology, Friedrich-Loeffler-Institut, Federal Research Institute for Animal Health, S├╝dufer 10, 17493 Greifswald - Insel Riems, Germany.
Departments of Anesthesiology, Medicine, and Surgery, Washington University School of Medicine, St Louis, 660 S. Euclid, St Louis, Missouri 63110, USA.
Department of Infectious Diseases, Molecular Virology, Heidelberg University, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany.
German Center for Infection Research (DZIF), Heidelberg Partner Site, Im Neuenheimer Feld 345, 69120 Heidelberg, Germany.
Division of Virus-Associated Carcinogenesis, German Cancer Research Center (DKFZ), Im Neuenheimer Feld 280, 69120 Heidelberg, Germany.


Despite the recent increase in the development of antivirals and antibiotics, antimicrobial resistance and the lack of broad-spectrum virus-targeting drugs are still important issues and additional alternative approaches to treat infectious diseases are urgently needed. Host-directed therapy (HDT) is an emerging approach in the field of anti-infectives. The strategy behind HDT is to interfere with host cell factors that are required by a pathogen for replication or persistence, to enhance protective immune responses against a pathogen, to reduce exacerbated inflammation and to balance immune reactivity at sites of pathology. Although HDTs encompassing interferons are well established for the treatment of chronic viral hepatitis, novel strategies aimed at the functional cure of persistent viral infections and the development of broad-spectrum antivirals against emerging viruses seem to be crucial. In chronic bacterial infections, such as tuberculosis, HDT strategies aim to enhance the antimicrobial activities of phagocytes and to curtail inflammation through interference with soluble factors (such as eicosanoids and cytokines) or cellular factors (such as co-stimulatory molecules). This Review describes current progress in the development of HDTs for viral and bacterial infections, including sepsis, and the challenges in bringing these new approaches to the clinic.


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