PREVENTION OF RHINOVIRUS AND POLIOVIRUS UNCOATING BY WIN-51711, A NEW ANTIVIRAL DRUG
PREVENTION OF RHINOVIRUS AND POLIOVIRUS UNCOATING BY WIN-51711, A NEW ANTIVIRAL DRUG
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DOI：
10.1128/aac.30.1.110
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发表时间：
1986-07-01
影响因子：
4.9
通讯作者：
MCKINLAY, MA
中科院分区：
文献类型：
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作者：
FOX, MP;OTTO, MJ;MCKINLAY, MA
Win 51711是一种有效的新药，可抑制人脊髓灰质炎病毒2型和人2型鼻病毒复制周期中的一个早期事件。Win 51711没有致病作用，对[~3H]尿苷标记的病毒粒子在细胞上的吸附也没有明显影响。当通过丧失对中和抗血清的敏感性来确定病毒对质膜的穿透时，Win 51711对脊髓灰质炎病毒的穿透没有影响，但对鼻病毒的穿透抑制了40%。在Win 51711存在下，中性红包被病毒感染的细胞在感染后3h暴露在光照下，感染中心的数量减少了3个对数，这表明Win 51711在穿透细胞膜后保持了病毒核糖核酸的包埋状态。在中性红实验中，Win 51711对脱包被的抑制呈浓度依赖性，浓度为0.03ug/ml时，脱包被的抑制率为90%。[~3H]尿苷标记脊髓灰质炎病毒感染的全细胞裂解物蔗糖梯度沉淀法表明，在Win 51711存在下，脊髓灰质炎病毒粒子保持完整，但在没有药物的情况下，脊髓灰质炎病毒粒子没有被包被。Win 51711还防止了脊髓灰质炎病毒感染性的热灭活，表明该化合物对病毒衣壳构象具有直接稳定作用。
WIN 51711, a potent new antipicornavirus drug, has been shown to inhibit an early event in the replication cycle of human poliovirus type 2 and human rhinovirus type 2. WIN 51711 was not virucidal and had no measurable effect on the adsorption of [3H]uridine-labeled virions to cells. When virion penetration of the plasma membrane was determined through loss of sensitivity to neutralizing antisera, WIN 51711 had no effect on poliovirus penetration, but inhibited rhinovirus penetration by 40%. In the presence of WIN 51711, exposure of neutral red-encapsidated virus-infected cells to light at 3 h postinfection resulted in a 3-log reduction in the number of infectious centers, indicating that WIN 51711 maintained the viral RNA in the encapsidated state after penetrating the cell membrane. The inhibition of uncoating by WIN 51711 in the neutral red assay was found to be concentration dependent, with a concentration of 0.03 .mu.g/ml resulting in a 90% inhibition of uncoating. Sucrose gradient sedimentation of lysates from whole cells infected with [3H]uridine-labeled poliovirus showed tht poliovirions remained intact in the presence of WIN 51711, but were uncoated in the absence of drug. WIN 51711 also prevented thermal inactivation of poliovirus infectivity, indicating a direct stabilizing effect of this compound on virion capsid conformation.