Wong J P, Christopher M E, Salazar A M, Dale R M K, Sun L-Q, Wang M
Defence R&D Canada - Suffield, Ralston, AB, Canada.
Vaccine. 2007 Apr 20;25(16):3175-8. doi: 10.1016/j.vaccine.2007.01.051. Epub 2007 Jan 19.
Influenza viruses are etiological agents of deadly flu that continue to pose global health threats, and have caused global pandemics that killed millions of people worldwide. The availability of neuraminidase inhibitors and attenuated vaccines improves our ability to defend against influenza, but their benefits can be significantly limited by drug-resistance and virus mutations. Nucleic acid-based drugs may represent a promising class of antiviral agents that could play a role in the prevention and treatment of influenza. Efficacy studies in animals have shown that ds RNA, such as poly ICLC can provide effective and broad-spectrum prophylaxis against lethal challenges against various strains of influenza A virus. Furthermore, similar level of antiviral protection in mice can be provided by using short fragments of oligonucleotides that induce antiviral immunity. Finally, influenza virus expression can also be specifically inhibited or suppressed using antisense oligonucleotides that bind to viral mRNA encoding key viral proteins. The versatility and potency of nucleic acid-based drugs make them potential drug candidates for used in seasonal or pandemic influenza situations.
流感病毒是致命流感的病原体,持续对全球健康构成威胁,并引发了导致全球数百万人死亡的全球大流行。神经氨酸酶抑制剂和减毒疫苗的出现提高了我们抵御流感的能力,但耐药性和病毒突变可能会显著限制它们的效果。基于核酸的药物可能是一类有前景的抗病毒药物,可在流感的预防和治疗中发挥作用。动物实验研究表明,双链RNA,如聚肌胞苷酸,可针对各种甲型流感病毒毒株的致命攻击提供有效且广谱的预防作用。此外,使用能诱导抗病毒免疫的寡核苷酸短片段,也可为小鼠提供类似水平的抗病毒保护。最后,通过与编码关键病毒蛋白的病毒mRNA结合的反义寡核苷酸,还可特异性抑制或压制流感病毒的表达。基于核酸的药物的多功能性和有效性使其成为季节性或大流行性流感情况下的潜在候选药物。