RT Journal Article
SR Electronic
T1 Astrovirus Replication Is Inhibited by Nitazoxanide <em>In Vitro</em> and <em>In Vivo</em>
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 797316
DO 10.1101/797316
A1 Virginia Hargest
A1 Bridgett Sharp
A1 Brandi Livingston
A1 Valerie Cortez
A1 Stacey Schultz-Cherry
YR 2019
UL http://biorxiv.org/content/early/2019/10/08/797316.abstract
AB Astroviruses (AstV) are a leading cause of diarrhea especially in the very young, the elderly, and immunocompromised populations. Despite their significant impact on public health, no drug therapies for astrovirus have been identified. In this study we fill this gap in knowledge and demonstrate that the FDA-approved broad-spectrum anti-infective drug nitazoxanide (NTZ) blocks astrovirus replication in vitro with a 50% effective concentration (EC50) of approximately 1.47μM. It can be administered up to 8 hours post-infection and is effective against multiple human astrovirus serotypes including clinical isolates. Most importantly, NTZ reduces viral shed and clinical disease (diarrhea) in vivo, exhibiting its potential as a future clinical therapeutic.Importance Human astroviruses (HAstV) are thought to cause between 2 and 9% of acute, non-bacterial diarrhea cases in children worldwide. HAstV infection can be especially problematic in immunocompromised people and infants where the virus has been associated with necrotizing enterocolitis, severe and persistent diarrhea, as well as systemic and often fatal disease. Yet no antivirals have been identified to treat astrovirus infection. Our study provides the first evidence that nitazoxanide may be an effective therapeutic strategy against astrovirus disease.