Astrovirus Replication Is Inhibited by Nitazoxanide In Vitro and In Vivo
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 th...
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creator | Hargest, Virginia Sharp, Bridgett Livingston, Brandi Cortez, Valerie Schultz-Cherry, Stacey |
description | 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
with a 50% effective concentration (EC
) of approximately 1.47 μM. It can be administered up to 8 h postinfection and is effective against multiple human astrovirus serotypes, including clinical isolates. Most importantly, NTZ reduces viral shedding
, exhibiting its potential as a future clinical therapeutic.
Human astroviruses (HAstV) are thought to cause between 2 and 9% of acute, nonbacterial 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 and severe and persistent diarrhea, as well as rare instances of systemic and fatal disease. And 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. |
doi_str_mv | 10.1128/JVI.01706-19 |
format | Article |
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with a 50% effective concentration (EC
) of approximately 1.47 μM. It can be administered up to 8 h postinfection and is effective against multiple human astrovirus serotypes, including clinical isolates. Most importantly, NTZ reduces viral shedding
, exhibiting its potential as a future clinical therapeutic.
Human astroviruses (HAstV) are thought to cause between 2 and 9% of acute, nonbacterial 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 and severe and persistent diarrhea, as well as rare instances of systemic and fatal disease. And 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.</description><identifier>ISSN: 0022-538X</identifier><identifier>EISSN: 1098-5514</identifier><identifier>DOI: 10.1128/JVI.01706-19</identifier><identifier>PMID: 31776285</identifier><language>eng</language><publisher>United States: American Society for Microbiology</publisher><subject>Animals ; Astroviridae Infections - drug therapy ; Astroviridae Infections - virology ; Caco-2 Cells ; Cell Survival - drug effects ; Diarrhea - virology ; Enterocolitis, Necrotizing - drug therapy ; Enterocolitis, Necrotizing - virology ; Humans ; Mamastrovirus - drug effects ; Mamastrovirus - immunology ; Poultry ; Thiazoles - antagonists & inhibitors ; Vaccines and Antiviral Agents ; Virus Replication - drug effects ; Virus Replication - physiology</subject><ispartof>Journal of virology, 2020-02, Vol.94 (5)</ispartof><rights>Copyright © 2020 American Society for Microbiology.</rights><rights>Copyright © 2020 American Society for Microbiology. 2020 American Society for Microbiology</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c384t-d01972e5ae50000dfcf33af18da1e8d86acf36c9ece08205d462365505cdb5cd3</citedby><cites>FETCH-LOGICAL-c384t-d01972e5ae50000dfcf33af18da1e8d86acf36c9ece08205d462365505cdb5cd3</cites></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7022343/pdf/$$EPDF$$P50$$Gpubmedcentral$$H</linktopdf><linktohtml>$$Uhttps://www.ncbi.nlm.nih.gov/pmc/articles/PMC7022343/$$EHTML$$P50$$Gpubmedcentral$$H</linktohtml><link.rule.ids>230,314,723,776,780,881,27901,27902,53766,53768</link.rule.ids><backlink>$$Uhttps://www.ncbi.nlm.nih.gov/pubmed/31776285$$D View this record in MEDLINE/PubMed$$Hfree_for_read</backlink></links><search><creatorcontrib>Hargest, Virginia</creatorcontrib><creatorcontrib>Sharp, Bridgett</creatorcontrib><creatorcontrib>Livingston, Brandi</creatorcontrib><creatorcontrib>Cortez, Valerie</creatorcontrib><creatorcontrib>Schultz-Cherry, Stacey</creatorcontrib><title>Astrovirus Replication Is Inhibited by Nitazoxanide In Vitro and In Vivo</title><title>Journal of virology</title><addtitle>J Virol</addtitle><description>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
with a 50% effective concentration (EC
) of approximately 1.47 μM. It can be administered up to 8 h postinfection and is effective against multiple human astrovirus serotypes, including clinical isolates. Most importantly, NTZ reduces viral shedding
, exhibiting its potential as a future clinical therapeutic.
Human astroviruses (HAstV) are thought to cause between 2 and 9% of acute, nonbacterial 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 and severe and persistent diarrhea, as well as rare instances of systemic and fatal disease. And 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.</description><subject>Animals</subject><subject>Astroviridae Infections - drug therapy</subject><subject>Astroviridae Infections - virology</subject><subject>Caco-2 Cells</subject><subject>Cell Survival - drug effects</subject><subject>Diarrhea - virology</subject><subject>Enterocolitis, Necrotizing - drug therapy</subject><subject>Enterocolitis, Necrotizing - virology</subject><subject>Humans</subject><subject>Mamastrovirus - drug effects</subject><subject>Mamastrovirus - immunology</subject><subject>Poultry</subject><subject>Thiazoles - antagonists & inhibitors</subject><subject>Vaccines and Antiviral Agents</subject><subject>Virus Replication - drug effects</subject><subject>Virus Replication - physiology</subject><issn>0022-538X</issn><issn>1098-5514</issn><fulltext>true</fulltext><rsrctype>article</rsrctype><creationdate>2020</creationdate><recordtype>article</recordtype><sourceid>EIF</sourceid><recordid>eNpVkN1LwzAUxYMobk7ffJY--mBnPtv0RRhDXWUoiA7fQpqkLtI1s2mH8683ujn0Qrgk5-Tcyw-AUwSHCGF-eTfLhxClMIlRtgf6CGY8ZgzRfdCHEOOYEf7SA0fev0GIKE3oIegRlKYJ5qwPJiPfNm5lm85Hj2ZZWSVb6-oo91Fez21hW6OjYh3d21Z-ug9ZW22CEs1s-BbJWm8uK3cMDkpZeXOy7QPwfHP9NJ7E04fbfDyaxopw2sYaoizFhknDYChdqpIQWSKuJTJc80SGh0RlRhnIMWSaJpgkjEGmdBEOGYCrTe6yKxZGK1O3jazEsrEL2ayFk1b8V2o7F69uJdIAg1ASAs63AY1774xvxcJ6ZapK1sZ1XmCCMspTnqFgvdhYVeO8b0y5G4Og-IYvAnzxA1-gLNjP_q62M__SJl8PwICJ</recordid><startdate>20200214</startdate><enddate>20200214</enddate><creator>Hargest, Virginia</creator><creator>Sharp, Bridgett</creator><creator>Livingston, Brandi</creator><creator>Cortez, Valerie</creator><creator>Schultz-Cherry, Stacey</creator><general>American Society for Microbiology</general><scope>CGR</scope><scope>CUY</scope><scope>CVF</scope><scope>ECM</scope><scope>EIF</scope><scope>NPM</scope><scope>AAYXX</scope><scope>CITATION</scope><scope>7X8</scope><scope>5PM</scope></search><sort><creationdate>20200214</creationdate><title>Astrovirus Replication Is Inhibited by Nitazoxanide In Vitro and In Vivo</title><author>Hargest, Virginia ; Sharp, Bridgett ; Livingston, Brandi ; Cortez, Valerie ; Schultz-Cherry, Stacey</author></sort><facets><frbrtype>5</frbrtype><frbrgroupid>cdi_FETCH-LOGICAL-c384t-d01972e5ae50000dfcf33af18da1e8d86acf36c9ece08205d462365505cdb5cd3</frbrgroupid><rsrctype>articles</rsrctype><prefilter>articles</prefilter><language>eng</language><creationdate>2020</creationdate><topic>Animals</topic><topic>Astroviridae Infections - drug therapy</topic><topic>Astroviridae Infections - virology</topic><topic>Caco-2 Cells</topic><topic>Cell Survival - drug effects</topic><topic>Diarrhea - virology</topic><topic>Enterocolitis, Necrotizing - drug therapy</topic><topic>Enterocolitis, Necrotizing - virology</topic><topic>Humans</topic><topic>Mamastrovirus - drug effects</topic><topic>Mamastrovirus - immunology</topic><topic>Poultry</topic><topic>Thiazoles - antagonists & inhibitors</topic><topic>Vaccines and Antiviral Agents</topic><topic>Virus Replication - drug effects</topic><topic>Virus Replication - physiology</topic><toplevel>peer_reviewed</toplevel><toplevel>online_resources</toplevel><creatorcontrib>Hargest, Virginia</creatorcontrib><creatorcontrib>Sharp, Bridgett</creatorcontrib><creatorcontrib>Livingston, Brandi</creatorcontrib><creatorcontrib>Cortez, Valerie</creatorcontrib><creatorcontrib>Schultz-Cherry, Stacey</creatorcontrib><collection>Medline</collection><collection>MEDLINE</collection><collection>MEDLINE (Ovid)</collection><collection>MEDLINE</collection><collection>MEDLINE</collection><collection>PubMed</collection><collection>CrossRef</collection><collection>MEDLINE - Academic</collection><collection>PubMed Central (Full Participant titles)</collection><jtitle>Journal of virology</jtitle></facets><delivery><delcategory>Remote Search Resource</delcategory><fulltext>fulltext</fulltext></delivery><addata><au>Hargest, Virginia</au><au>Sharp, Bridgett</au><au>Livingston, Brandi</au><au>Cortez, Valerie</au><au>Schultz-Cherry, Stacey</au><format>journal</format><genre>article</genre><ristype>JOUR</ristype><atitle>Astrovirus Replication Is Inhibited by Nitazoxanide In Vitro and In Vivo</atitle><jtitle>Journal of virology</jtitle><addtitle>J Virol</addtitle><date>2020-02-14</date><risdate>2020</risdate><volume>94</volume><issue>5</issue><issn>0022-538X</issn><eissn>1098-5514</eissn><abstract>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
with a 50% effective concentration (EC
) of approximately 1.47 μM. It can be administered up to 8 h postinfection and is effective against multiple human astrovirus serotypes, including clinical isolates. Most importantly, NTZ reduces viral shedding
, exhibiting its potential as a future clinical therapeutic.
Human astroviruses (HAstV) are thought to cause between 2 and 9% of acute, nonbacterial 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 and severe and persistent diarrhea, as well as rare instances of systemic and fatal disease. And 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.</abstract><cop>United States</cop><pub>American Society for Microbiology</pub><pmid>31776285</pmid><doi>10.1128/JVI.01706-19</doi><oa>free_for_read</oa></addata></record> |
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subjects | Animals Astroviridae Infections - drug therapy Astroviridae Infections - virology Caco-2 Cells Cell Survival - drug effects Diarrhea - virology Enterocolitis, Necrotizing - drug therapy Enterocolitis, Necrotizing - virology Humans Mamastrovirus - drug effects Mamastrovirus - immunology Poultry Thiazoles - antagonists & inhibitors Vaccines and Antiviral Agents Virus Replication - drug effects Virus Replication - physiology |
title | Astrovirus Replication Is Inhibited by Nitazoxanide In Vitro and In Vivo |
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