Werner G H
Institut de chimie des substances naturelles, CNRS, Gif-sur-Yvette.
Bull Acad Natl Med. 1992 May;176(5):669-81.
Rhinoviruses are the main etiologic agents of infectious common colds, which represent about 40% of the acute respiratory infections in man. The antigenic diversity of rhinoviruses precludes any prevention by vaccination. Within the last 20 years, efforts have therefore concentrated on chemoprophylaxis or chemotherapy with antiviral agents. Interferons (alpha and beta) administered intranasally at high doses, exerted a significant prophylactic activity in volunteers inoculated with rhinoviruses or in the course of epidemics in families. By contrast, the therapeutic activity of interferons is almost nonexistent, which greatly limits their practical interest. Various synthetic chemicals exert a marked and selective inhibitory effect on the replication of various serotypes of rhinoviruses in cell cultures. In the absence of an animal model of rhinovirus infection, in vivo studies of these molecules have been performed in human volunteers, chiefly at the Common Cold Research Unit in Salisbury (Great Britain). 3 synthetic compounds (an imidazothiazole, a benzimidazole derivative and a piperazinyl-pyridazine) have exerted a significant prophylactic activity, especially marked with the latter. None of these compounds, however, was active when administered after the infectious challenge. The search for selective anti-rhinovirus compounds is still going on; it will probably be facilitated through a combination of structural studies of rhinovirus capsids (or of their cellular receptors) with computer-assisted design of synthetic molecules. The recent observation of the influence of psychological factors on the propensity of rhinovirus-infected subjects to develop clinically apparent common cold must be taken into account in future studies.
鼻病毒是传染性普通感冒的主要病原体,普通感冒约占人类急性呼吸道感染的40%。鼻病毒的抗原多样性使得无法通过疫苗进行预防。因此,在过去20年里,工作集中在使用抗病毒药物进行化学预防或化疗。高剂量鼻内给予干扰素(α和β),在接种鼻病毒的志愿者或家庭流行期间发挥了显著的预防作用。相比之下,干扰素的治疗作用几乎不存在,这极大地限制了它们的实际应用价值。各种合成化学物质对细胞培养中各种血清型鼻病毒的复制具有显著的选择性抑制作用。由于缺乏鼻病毒感染的动物模型,这些分子的体内研究主要在英国索尔兹伯里的普通感冒研究单位的人类志愿者中进行。3种合成化合物(一种咪唑噻唑、一种苯并咪唑衍生物和一种哌嗪基哒嗪)发挥了显著的预防作用,尤其是后者更为明显。然而,这些化合物在感染攻击后给药时均无活性。对选择性抗鼻病毒化合物的研究仍在继续;通过结合鼻病毒衣壳(或其细胞受体)的结构研究与合成分子的计算机辅助设计,可能会促进这一研究。在未来的研究中必须考虑到最近观察到的心理因素对鼻病毒感染受试者发生临床明显普通感冒倾向的影响。