Davis Alicia M, Chabolla Bryan J, Newcomb Laura L
Department of Biology, California State University San Bernardino, 5500 University Parkway, San Bernardino, CA 92407, USA.
Virol J. 2014 Sep 16;11:167. doi: 10.1186/1743-422X-11-167.
Emerging antiviral resistant strains of influenza A virus are greatly limiting the therapies available to stop aggressive infections. Genome changes that confer resistance to the two classes of approved antivirals have been identified in circulating influenza A viruses. It is only a matter of time before the currently approved influenza A antivirals are rendered ineffective, emphasizing the need for additional influenza antiviral therapies. This review highlights the current state of antiviral resistance in circulating and highly pathogenic influenza A viruses and explores potential antiviral targets within the proteins of the influenza A virus ribonucleoprotein (vRNP) complex, drawing attention to the viral protein activities and interactions that play an indispensable role in the influenza life cycle. Investigation of small molecule inhibition, accelerated by the use of crystal structures of vRNP proteins, has provided important information about viral protein domains and interactions, and has revealed many promising antiviral drug candidates discussed in this review.
甲型流感病毒不断出现的抗病毒耐药菌株极大地限制了用于阻止侵袭性感染的可用治疗方法。在流行的甲型流感病毒中已发现赋予对两类已批准抗病毒药物耐药性的基因组变化。目前批准的甲型流感抗病毒药物失效只是时间问题，这凸显了对额外甲型流感抗病毒疗法的需求。本综述重点介绍了流行和高致病性甲型流感病毒中抗病毒耐药性的现状，并探讨了甲型流感病毒核糖核蛋白（vRNP）复合体蛋白质中的潜在抗病毒靶点，提请关注在流感病毒生命周期中起不可或缺作用的病毒蛋白活性和相互作用。利用vRNP蛋白的晶体结构加速的小分子抑制研究，提供了有关病毒蛋白结构域和相互作用的重要信息，并揭示了本综述中讨论的许多有前景的抗病毒药物候选物。
