Broad-spectrum antiviral that interferes with de novo pyrimidine biosynthesis

• Published in: Proceedings of the National Academy of Sciences - PNAS Vol. 108; no. 14; pp. 5777 - 5782
• Main Authors: Hoffmann, Hans-Heinrich, Kunz, Andrea, Simon, Viviana A, Palese, Peter, Shaw, Megan L
• Format: Journal Article
• Language: English
• Published: United States National Academy of Sciences 05.04.2011; National Acad Sciences
• Subjects: Animals; Antiviral Agents - pharmacology; antiviral properties; Antivirals; Autoradiography; Avian orthoavulavirus 1; beta-Galactosidase - metabolism; Biological Sciences; Biosynthesis; Carbamates; Cell Line, Tumor; Cell lines; Cell Survival - drug effects; Cells; Chickens; Dengue virus; Deoxyribonucleic acid; DNA; DNA Primers - genetics; Epithelial cells; Hepatitis C virus; Human adenovirus; Human immunodeficiency virus; Humans; Indoles - pharmacology; Influenza virus; Inhibitory concentration 50; Lamivudine; Mammals; Nevirapine; Newcastle disease; Newcastle disease virus; orotic acid; Orthomyxoviridae; Oxadiazoles - pharmacology; Oxidoreductases Acting on CH-CH Group Donors - metabolism; Proteins; Pyrimidines; Pyrimidines - biosynthesis; Pyrimidines - metabolism; Pyrrolidinones; Raltegravir Potassium; Retrovirus; Ribonucleic acid; RNA; Sindbis virus; Species Specificity; Sulfonamides; Time Factors; uracil; Vaccinia virus; Vector-borne diseases; Vero cells; vertebrate viruses; Vesicular stomatitis virus; Vesiculovirus; virus replication; Virus Replication - drug effects; Viruses; Viruses - drug effects; Viruses - growth & development; West Nile virus

Compound A3 was identified in a high-throughput screen for inhibitors of influenza virus replication. It displays broad-spectrum antiviral activity, and at noncytotoxic concentrations it is shown to inhibit the replication of negative-sense RNA viruses (influenza viruses A and B, Newcastle disease v...