Huraux J M, Ingrand D, Agut H, Devillechabrolle A
Lab. de Bactériologie-Virologie, Groupe Hospitalier Pitié-Salpétrière, Paris.
Rev Pneumol Clin. 1989;45(3):99-105.
The advances achieved in our knowledge on the virus multiplication cycle and the challenge created by the advent of AIDS have resulted in a rational development of new antiviral agents. However, antiviral chemotherapy is hindered by several obstacles: (1) most antiviral drugs are cytotoxic, with the exception of acyclovir which owes its remarkable safety to its activation by the thymidine kinase of the herpes simplex viruses and of the varicella-zoster virus; (2) the risk of selecting resistant strains by mutation of viral enzymes is the unavoidable price to pay for the specificity of new antiviral agents which interfere with these enzymes; so far, this risk seems to apply only to immunocompromised patients; (3) latent viral infection, defined as the lack of active multiplication of the virus, cannot be eradicated by the antiviral drugs available at present since these drugs are inhibitors of viral multiplication. However, anti-sens oligonucleotides could, at least in theory, be used to treat this type of infection which is not limited to the Retroviridae or Herpesviridae families. Finally, antiviral drugs active against life-threatening infections that are as common as rabies and the severe forms of measles or viral hepatitis remain to be discovered.
我们对病毒增殖周期的认识取得的进展以及艾滋病出现所带来的挑战,促使了新型抗病毒药物的合理研发。然而,抗病毒化疗面临着几个障碍:(1)大多数抗病毒药物具有细胞毒性,阿昔洛韦除外,它因其由单纯疱疹病毒和水痘 - 带状疱疹病毒的胸苷激酶激活而具有显著的安全性;(2)通过病毒酶突变选择耐药菌株的风险是新型抗病毒药物特异性所不可避免要付出的代价,这些药物会干扰这些酶;到目前为止,这种风险似乎仅适用于免疫功能低下的患者;(3)潜伏性病毒感染,定义为病毒缺乏活跃增殖,目前可用的抗病毒药物无法根除,因为这些药物是病毒增殖的抑制剂。然而,反义寡核苷酸至少在理论上可用于治疗这种不限于逆转录病毒科或疱疹病毒科的感染类型。最后,针对如狂犬病、严重麻疹或病毒性肝炎等常见的危及生命感染的抗病毒药物仍有待发现。