Effective Oral Favipiravir (T-705) Therapy Initiated after the Onset of Clinical Disease in a Model of Arenavirus Hemorrhagic Fever 英文参考文献.docVIP

下载本文档

5
0
约4.93万字
约 10页
2017-05-11 发布于上海
举报
版权申诉

Effective Oral Favipiravir (T-705) Therapy Initiated after the Onset of Clinical Disease in a Model of Arenavirus Hemorrhagic Fever 英文参考文献.doc

1、本文档共10页，可阅读全部内容。
2、原创力文档（book118）网站文档一经付费（服务费），不意味着购买了该文档的版权，仅供个人/单位学习、研究之用，不得用于商业用途，未经授权，严禁复制、发行、汇编、翻译或者网络传播等，侵权必究。
3、本站所有内容均由合作方或网友上传，本站不对文档的完整性、权威性及其观点立场正确性做任何保证或承诺！文档内容仅供研究参考，付费前请自行鉴别。如您付费，意味着您自己接受本站规则且自行承担风险，本站不退款、不进行额外附加服务；查看《如何避免下载的几个坑》。如果您已付费下载过本站文档，您可以点击这里二次下载。
4、如文档侵犯商业秘密、侵犯著作权、侵犯人身权等，请点击“版权申诉”（推荐），也可以打举报电话：400-050-0827(电话支持时间：9:00-18:30)。
5、该文档为VIP文档，如果想要下载，成为VIP会员后，下载免费。
6、成为VIP后，下载本文档将扣除1次下载权益。下载后，不支持退款、换文档。如有疑问请联系我们。
7、成为VIP后，您将拥有八大权益，权益包括：VIP文档下载权益、阅读免打扰、文档格式转换、高级专利检索、专属身份标志、高级客服、多端互通、版权登记。
8、VIP文档为合作方或网友上传，每下载1次，网站将根据用户上传文档的质量评分、类型等，对文档贡献者给予高额补贴、流量扶持。如果你也想贡献VIP文档。上传文档

Effective Oral Favipiravir (T-705) Therapy Initiated after the Onset of Clinical Disease in a Model of Arenavirus Hemorrhagic Fever 英文参考文献

EffectiveOralFavipiravir(T-705)TherapyInitiatedafter theOnsetofClinicalDiseaseinaModelofArenavirus HemorrhagicFever MichelleMendenhall1,AndrewRussell1,DonaldF.Smee1,JefferyO.Hall1,RamonaSkirpstunas1,2, YousukeFuruta3,BrianB.Gowen1* 1DepartmentofAnimal,Dairy,andVeterinarySciences,UtahStateUniversity,Logan,Utah,UnitedStatesofAmerica,2DepartmentofAgricultureandFood,Stateof Utah,Logan,Utah,UnitedStatesofAmerica,3ResearchLaboratories,ToyamaChemicalCompany,Ltd.,Toyama,Japan Abstract Background:LassaandJun?′nvirusesarethemostprominentmembersoftheArenaviridaefamilyofvirusesthatcauseviral hemorrhagicfeversyndromesLassafeverandArgentinehemorrhagicfever,respectively.Atpresent,ribavirinistheonly antiviral drug indicated for use in treatment of these diseases, but because of its limited efficacy in advanced cases of diseaseanditstoxicity,saferandmoreeffectiveantiviralsareneeded. Methodology/Principal Findings: Here, we used a model of acute arenaviral infection in outbred guinea pigs based on challenge with an adapted strain of Pichinde′ virus (PICV) to further preclinical development of T-705 (Favipiravir), a promisingbroad-spectruminhibitorofRNAvirusinfections.Theguineapig-adaptedpassage19PICVwasuniformlylethal with an LD50 of ,5 plaque-forming units and disease was associated with fever, weight loss, thrombocytopenia, coagulation defects, increases in serum aspartate aminotransferase (AST) concentrations, and pantropic viral infection. Favipiravir (300mg/kg/day, twice daily orally for 14 days) was highly effective, as all animals recovered fully from PICV- induceddiseaseevenwhentherapywasinitiatedoneweekafterviruschallengewhenanimalswerealreadysignificantlyill with marked fevers and thrombocytopenia. Antiviral activity and reduced disease severity was evidenced by dramatic reductionsinpeakserumvirustitersandASTconcentrationsinfavipiravir-treatedanimals.Moreover,asharpdecreasein body temperature was observed shortly after the start of treatment. Oral ribavirin was also evalu