Treatment of norovirus infections: Moving antivirals from the bench to the bedside

• Published in: Antiviral research Vol. 105; pp. 80 - 91
• Main Authors: Kaufman, Stuart S., Green, Kim Y., Korba, Brent E.
• Format: Journal Article
• Language: English
• Published: Kidlington Elsevier B.V 01.05.2014; Elsevier
• Subjects: Antibiotics. Antiinfectious agents. Antiparasitic agents; Antiviral; Antiviral agents; Antiviral Agents - isolation & purification; Antiviral Agents - therapeutic use; Biological and medical sciences; Biomarkers - analysis; Caliciviridae Infections - drug therapy; Caliciviridae Infections - pathology; Clinical Trials as Topic; Diarrhea; Drug Evaluation, Preclinical - methods; Drug Monitoring - methods; Drug treatment; Gastroenterology. Liver. Pancreas. Abdomen; Global Health; Humans; Immunocompromised; Immunocompromised Host; Immunodeficiencies; Immunodeficiencies. Immunoglobulinopathies; Immunopathology; Medical sciences; Norovirus; Norovirus - drug effects; Other diseases. Semiology; Pharmacology. Drug treatments; Stomach. Duodenum. Small intestine. Colon. Rectum. Anus; Transplant; United States - epidemiology; United States; Diarrhea; Antiviral; Norovirus; Drug treatment; Immunocompromised; Transplant; Drug; Immunopathology; Transplantation; Immune deficiency; Virus; Infection; Immunosuppression; Treatment; Caliciviridae; Digestive diseases; Intestinal disease
• ISSN: 0166-3542; 1872-9096
• DOI: 10.1016/j.antiviral.2014.02.012

•Norovirus (NV) illness in transplant recipients can be life-threatening, requiring intensive supportive care.•Clinical and laboratory features of NV illness in immunocompromised patients are reviewed.•Potential design and features of clinical trials in immunocompromised patients are described.•How effective trials in these patients might be used in the setting of acute outbreaks is discussed.•The current status of anti-NV drug discovery is reviewed. Noroviruses (NV) are the most common cause of acute gastrointestinal illness in the United States and worldwide. The development of specific antiviral countermeasures has lagged behind that of other viral pathogens, primarily because norovirus disease has been perceived as brief and self-limiting and robust assays suitable for drug discovery have been lacking. The increasing recognition that NV illness can be life-threatening, especially in immunocompromised patients who often require prolonged hospitalization and intensive supportive care, has stimulated new research to develop an effective antiviral therapy. Here, we propose a path forward for evaluating drug therapy in norovirus-infected immunocompromised individuals, a population at high risk for serious and prolonged illness. The clinical and laboratory features of norovirus illness in immunocompromised patients are reviewed, and potential markers of drug efficacy are defined. We discuss the potential design of clinical trials in these patients and how an antiviral therapy that proves effective in immunocompromised patients might also be used in the setting of acute outbreaks, especially in confined settings such as nursing homes, to block the spread of infection and reduce the severity of illness. We conclude by reviewing the current status of approved and experimental compounds that might be evaluated in a hospital setting.