神经氨酸酶
病毒学
扎那米韦
奥司他韦
病毒
神经氨酸酶抑制剂
生物
甲型流感病毒
氨基酸取代
遗传学
医学
基因
突变
2019年冠状病毒病(COVID-19)
疾病
病理
传染病(医学专业)
作者
Elena A. Govorkova,Emi Takashita,Rod S. Daniels,Seiichiro Fujisaki,Lance Presser,Mira C. Patel,Jing‐Kai Huang,Angie Lackenby,Ha Nguyen,Dmitriy Pereyaslov,Áine Rattigan,Sook Kwan Brown,Magdi Samaan,Kanta Subbarao,Sun Wong,Dayan Wang,Richard J. Webby,Hui‐Ling Yen,Wenqing Zhang,Adam Meijer,Larisa V. Gubareva
标识
DOI:10.1016/j.antiviral.2022.105281
摘要
Global analysis of the susceptibility of influenza viruses to neuraminidase (NA) inhibitors (NAIs) and the polymerase acidic (PA) inhibitor (PAI) baloxavir was conducted by five World Health Organization Collaborating Centres for Reference and Research on Influenza during two periods (May 2018-May 2019 and May 2019-May 2020). Combined phenotypic and NA sequence-based analysis revealed that the global frequency of viruses displaying reduced or highly reduced inhibition (RI or HRI) or potential to show RI/HRI by NAIs remained low, 0.5% (165/35045) and 0.6% (159/26010) for the 2018-2019 and 2019-2020 periods, respectively. The most common amino acid substitution was NA-H275Y (N1 numbering) conferring HRI by oseltamivir and peramivir in A(H1N1)pdm09 viruses. Combined phenotypic and PA sequence-based analysis showed that the global frequency of viruses showing reduced susceptibility to baloxavir or carrying substitutions associated with reduced susceptibility was low, 0.5% (72/15906) and 0.1% (18/15692) for the 2018-2019 and 2019-2020 periods, respectively. Most (n = 61) of these viruses had I38→T/F/M/S/L/V PA amino acid substitutions. In Japan, where baloxavir use was highest, the rate was 4.5% (41/919) in the 2018-2019 period and most of the viruses (n = 32) had PA-I38T. Zoonotic viruses isolated from humans (n = 32) in different countries did not contain substitutions in NA associated with NAI RI/HRI phenotypes. One A(H5N6) virus had a dual substitution PA-I38V + PA-E199G, which may reduce susceptibility to baloxavir. Therefore, NAIs and baloxavir remain appropriate choices for the treatment of influenza virus infections, but close monitoring of antiviral susceptibility is warranted.
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