{"title":"针对肠道病毒 71 的再利用药物的体外协同抗病毒活性。","authors":"Kunlakanya Jitobaom, Chompunuch Boonarkart, Songkran Thongon, Thanyaporn Sirihongthong, Arpakorn Sornwong, Prasert Auewarakul, Ornpreya Suptawiwat","doi":"10.1007/s00705-024-06097-1","DOIUrl":null,"url":null,"abstract":"<div><p>Enteroviruses cause viral diseases that are harmful to children. Hand, foot, and mouth disease (HFMD) with neurological complications is mainly caused by enterovirus 71 (EV71). Despite its clinical importance, there is no effective antiviral drug against EV71. However, several repurposed drugs have been shown to have antiviral activity against related viruses. Treatments with single drugs and two-drug combinations were performed <i>in vitro</i> to assess anti-EV71 activity. Three repurposed drug candidates with broad-spectrum antiviral activity were found to demonstrate potent anti-EV71 activity: prochlorperazine, niclosamide, and itraconazole. To improve antiviral activity, combinations of two drugs were tested. Niclosamide and itraconazole showed synergistic antiviral activity in Vero cells, whereas combinations of niclosamide-prochlorperazine and itraconazole-prochlorperazine showed only additive effects. Furthermore, the combination of itraconazole and prochlorperazine showed an additive effect in neuroblastoma cells. Itraconazole and prochlorperazine exert their antiviral activities by inhibiting Akt phosphorylation. Repurposing of drugs can provide a treatment solution for HFMD, and our data suggest that combining these drugs can enhance that efficacy.</p></div>","PeriodicalId":8359,"journal":{"name":"Archives of Virology","volume":"169 8","pages":""},"PeriodicalIF":2.5000,"publicationDate":"2024-07-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"In vitro synergistic antiviral activity of repurposed drugs against enterovirus 71\",\"authors\":\"Kunlakanya Jitobaom, Chompunuch Boonarkart, Songkran Thongon, Thanyaporn Sirihongthong, Arpakorn Sornwong, Prasert Auewarakul, Ornpreya Suptawiwat\",\"doi\":\"10.1007/s00705-024-06097-1\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div><p>Enteroviruses cause viral diseases that are harmful to children. Hand, foot, and mouth disease (HFMD) with neurological complications is mainly caused by enterovirus 71 (EV71). Despite its clinical importance, there is no effective antiviral drug against EV71. However, several repurposed drugs have been shown to have antiviral activity against related viruses. Treatments with single drugs and two-drug combinations were performed <i>in vitro</i> to assess anti-EV71 activity. Three repurposed drug candidates with broad-spectrum antiviral activity were found to demonstrate potent anti-EV71 activity: prochlorperazine, niclosamide, and itraconazole. To improve antiviral activity, combinations of two drugs were tested. Niclosamide and itraconazole showed synergistic antiviral activity in Vero cells, whereas combinations of niclosamide-prochlorperazine and itraconazole-prochlorperazine showed only additive effects. Furthermore, the combination of itraconazole and prochlorperazine showed an additive effect in neuroblastoma cells. Itraconazole and prochlorperazine exert their antiviral activities by inhibiting Akt phosphorylation. Repurposing of drugs can provide a treatment solution for HFMD, and our data suggest that combining these drugs can enhance that efficacy.</p></div>\",\"PeriodicalId\":8359,\"journal\":{\"name\":\"Archives of Virology\",\"volume\":\"169 8\",\"pages\":\"\"},\"PeriodicalIF\":2.5000,\"publicationDate\":\"2024-07-30\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Archives of Virology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://link.springer.com/article/10.1007/s00705-024-06097-1\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q3\",\"JCRName\":\"VIROLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of Virology","FirstCategoryId":"3","ListUrlMain":"https://link.springer.com/article/10.1007/s00705-024-06097-1","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"VIROLOGY","Score":null,"Total":0}
In vitro synergistic antiviral activity of repurposed drugs against enterovirus 71
Enteroviruses cause viral diseases that are harmful to children. Hand, foot, and mouth disease (HFMD) with neurological complications is mainly caused by enterovirus 71 (EV71). Despite its clinical importance, there is no effective antiviral drug against EV71. However, several repurposed drugs have been shown to have antiviral activity against related viruses. Treatments with single drugs and two-drug combinations were performed in vitro to assess anti-EV71 activity. Three repurposed drug candidates with broad-spectrum antiviral activity were found to demonstrate potent anti-EV71 activity: prochlorperazine, niclosamide, and itraconazole. To improve antiviral activity, combinations of two drugs were tested. Niclosamide and itraconazole showed synergistic antiviral activity in Vero cells, whereas combinations of niclosamide-prochlorperazine and itraconazole-prochlorperazine showed only additive effects. Furthermore, the combination of itraconazole and prochlorperazine showed an additive effect in neuroblastoma cells. Itraconazole and prochlorperazine exert their antiviral activities by inhibiting Akt phosphorylation. Repurposing of drugs can provide a treatment solution for HFMD, and our data suggest that combining these drugs can enhance that efficacy.
期刊介绍：
Archives of Virology publishes original contributions from all branches of research on viruses, virus-like agents, and virus infections of humans, animals, plants, insects, and bacteria. Coverage spans a broad spectrum of topics, from descriptions of newly discovered viruses, to studies of virus structure, composition, and genetics, to studies of virus interactions with host cells, organisms and populations. Studies employ molecular biologic, molecular genetics, and current immunologic and epidemiologic approaches. Contents include studies on the molecular pathogenesis, pathophysiology, and genetics of virus infections in individual hosts, and studies on the molecular epidemiology of virus infections in populations. Also included are studies involving applied research such as diagnostic technology development, monoclonal antibody panel development, vaccine development, and antiviral drug development.Archives of Virology wishes to publish obituaries of recently deceased well-known virologists and leading figures in virology.
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