Acocal-Juárez Erick, Márquez-Domínguez Luis, Vallejo-Ruíz Verónica, Cedillo Lilia, Santos-López Gerardo
Centro de Investigaciones en Ciencias Microbiológicas, Benemérita Universidad Autónoma de Puebla, Puebla Pue, Mexico.
Laboratorio de Biología Molecular y Virología, Centro de Investigación Biomédica de Oriente, Instituto Mexicano del Seguro Social, Puebla, Mexico.
Drug Healthc Patient Saf. 2024 Sep 14;16:105-113. doi: 10.2147/DHPS.S470868. eCollection 2024.
Influenza control demands multifaceted strategies, including antiviral drugs. Baloxavir, a recent addition to influenza treatment, acts as an inhibitor of the Polymerase acid (PA) component of the viral polymerase. However, mutations associated with resistance have been identified.
This study analyzed PA gene sequences of influenza A and B viruses (IAV and IBV, respectively) reported in the Americas, retrieved from databases published until May 2023, to identify primary markers of resistance to baloxavir.
PA gene sequences were obtained from the GISAID and NCBI databases, focusing on countries in the Americas with 500 or more sequences for IAV, and 50 or more sequences for IBV.
Of the 58,816 PA sequences analyzed for IAV, only 55 (0.1%) harbored resistance markers, representing approximately 1 in 1000 occurrence. The most frequent markers were I38V (21 cases) and I38M (7 cases) at position 38 of PA, followed by E199G (9 cases) at position 199. For IBV, 14,684 sequences were analyzed, of which only eight presented a resistance marker (0.05%). Five sequences had the M34I marker, while the remaining three had the I38V marker. While frequency of resistance markers in PA is comparable to other regions, these results highlight the need for enhanced sequencing efforts, particularly in Latin America. Such efforts would serve to intensify influenza surveillance and inform public health interventions.
While baloxavir demonstrates efficacy against influenza, resistance markers have been identified, including pre-existing ones. Our study adds eight (IAV: six and IBV: two) new spontaneously occurring substitutions to the existing literature, highlighting the need for continued surveillance. Among these, I38M stands out due to its significant tenfold reduction in drug susceptibility. Therefore, vigilant monitoring of these resistance markers in IAV and IBV remains crucial for maintaining baloxavir's effectiveness and informing future public health interventions.
流感防控需要多方面策略，包括使用抗病毒药物。巴洛沙韦是近期用于流感治疗的药物，它作为病毒聚合酶的酸性聚合酶（PA）成分的抑制剂。然而，已发现与耐药性相关的突变。
本研究分析了从截至2023年5月发布的数据库中检索到的美洲地区报告的甲型和乙型流感病毒（分别为IAV和IBV）的PA基因序列，以确定对巴洛沙韦耐药的主要标志物。
PA基因序列从GISAID和NCBI数据库获取，重点关注美洲地区IAV序列数达500条或以上、IBV序列数达50条或以上的国家。
在分析的58816条IAV的PA序列中，仅有55条（0.1%）含有耐药标志物，发生率约为千分之一。最常见的标志物是PA第38位的I38V（21例）和I38M（7例），其次是第199位的E199G（9例）。对于IBV，分析了14684条序列，其中仅有8条呈现耐药标志物（0.05%）。5条序列有M34I标志物，其余3条有I38V标志物。虽然PA中耐药标志物的频率与其他地区相当，但这些结果凸显了加强测序工作的必要性，尤其是在拉丁美洲。此类工作将有助于加强流感监测并为公共卫生干预提供信息。
虽然巴洛沙韦对流感显示出疗效，但已发现耐药标志物，包括既往存在的标志物。我们的研究在现有文献基础上增加了8个（IAV：6个，IBV：2个）新的自发出现的替代突变位点，凸显了持续监测的必要性。其中，I38M因其药物敏感性显著降低十倍而格外突出。因此，对IAV和IBV中这些耐药标志物的密切监测对于维持巴洛沙韦的有效性以及为未来公共卫生干预提供信息仍然至关重要。
