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Global update on the susceptibilities of human influenza viruses to neuraminidase inhibitors and the cap-dependent endonuclease inhibitor baloxavir, 2017-2018.
Antiviral Research ( IF 7.6 ) Pub Date : 2020-01-28 , DOI: 10.1016/j.antiviral.2020.104718
Emi Takashita 1 , Rod S Daniels 2 , Seiichiro Fujisaki 1 , Vicki Gregory 2 , Larisa V Gubareva 3 , Weiijuan Huang 4 , Aeron C Hurt 5 , Angie Lackenby 6 , Ha T Nguyen 3 , Dmitriy Pereyaslov 7 , Merryn Roe 5 , Magdi Samaan 8 , Kanta Subbarao 5 , Herman Tse 9 , Dayan Wang 4 , Hui-Ling Yen 10 , Wenqing Zhang 8 , Adam Meijer 11
Affiliation  

The global analysis of neuraminidase inhibitor (NAI) susceptibility of influenza viruses has been conducted since the 2012-13 period. In 2018 a novel cap-dependent endonuclease inhibitor, baloxavir, that targets polymerase acidic subunit (PA) was approved for the treatment of influenza virus infection in Japan and the United States. For this annual report, the susceptibilities of influenza viruses to NAIs and baloxavir were analyzed. A total of 15409 viruses, collected by World Health Organization (WHO) recognized National Influenza Centers and other laboratories between May 2017 and May 2018, were assessed for phenotypic NAI susceptibility by five WHO Collaborating Centers (CCs). The 50% inhibitory concentration (IC50) was determined for oseltamivir, zanamivir, peramivir and laninamivir. Reduced inhibition (RI) or highly reduced inhibition (HRI) by one or more NAIs was exhibited by 0.8% of viruses tested (n = 122). The frequency of viruses with RI or HRI has remained low since this global analysis began (2012-13: 0.6%; 2013-14: 1.9%; 2014-15: 0.5%; 2015-16: 0.8%; 2016-17: 0.2%). PA gene sequence data, available from public databases (n = 13523), were screened for amino acid substitutions associated with reduced susceptibility to baloxavir (PA E23G/K/R, PA A36V, PA A37T, PA I38F/M/T/L, PA E119D, PA E199G): 11 (0.08%) viruses possessed such substitutions. Five of them were included in phenotypic baloxavir susceptibility analysis by two WHO CCs and IC50 values were determined. The PA variant viruses showed 6-17-fold reduced susceptibility to baloxavir. Overall, in the 2017-18 period the frequency of circulating influenza viruses with reduced susceptibility to NAIs or baloxavir was low, but continued monitoring is important.

中文翻译:

2017-2018年全球人类流感病毒对神经氨酸酶抑制剂和帽依赖性核酸内切酶抑制剂baloxavir敏感性的全球更新。

自2012-13年以来,已对流感病毒的神经氨酸酶抑制剂(NAI)敏感性进行了全球分析。在2018年,一种靶向聚合酶酸性亚基(PA)的新型帽依赖性核酸内切酶抑制剂baloxavir被批准用于日本和美国的流感病毒感染治疗。对于本年度报告,分析了流感病毒对NAI和baloxavir的敏感性。在2017年5月至2018年5月期间,世界卫生组织(WHO)认可的国家流感中心和其他实验室共收集了15409份病毒,并由五个WHO合作中心(CC)进行了表型NAI敏感性评估。测定了奥司他韦,扎那米韦,帕拉米韦和兰尼米韦的50%抑制浓度(IC50)。被测试的病毒的0.8%(n = 122)表现出一种或多种NAI降低的抑制(RI)或高度降低的抑制(HRI)。自这项全球分析开始以来,带有RI或HRI的病毒的频率一直很低(2012-13:0.6%; 2013-14:1.9%; 2014-15:0.5%; 2015-16:0.8%; 2016-17:0.2 %)。筛选了可从公共数据库(n = 13523)获得的PA基因序列数据,寻找与降低对baloxavir的敏感性相关的氨基酸取代(PA E23G / K / R,PA A36V,PA A37T,PA I38F / M / T / L, PA E119D,PA E199G):11种(0.08%)病毒拥有这种替代。通过两个WHO CC将其中五个纳入表型Baloxavir敏感性分析,并确定IC50值。PA变异病毒对baloxavir的敏感性降低了6-17倍。总体,
更新日期:2020-01-29
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