The picornavirus replication inhibitors HBB and guanidine in the echovirus-9 system: the significance of viral protein 2C
The picornavirus replication inhibitors HBB and guanidine in the echovirus-9 system: the significance of viral protein 2C
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DOI：
10.1099/0022-1317-81-4-895
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发表时间：
2000-04-01
影响因子：
3.8
通讯作者：
Nelsen-Salz, B
中科院分区：
文献类型：
--
作者：
Klein, M;Hadaschik, D;Nelsen-Salz, B
HBB [2-（α-羟基苄基）-苯并咪唑]和胍是小核糖核酸病毒复制的有效抑制剂。在其他证据中，有限的交叉耐药性和两种抑制剂的协同效应表明抗病毒作用的机制相似但不相同。对这些药物中的每一种耐药的埃可病毒-9变体进行了表征和测序。对六溴代二苯或胍的完全耐药性被证明是由于非结构蛋白2C中的单一但不同的点突变。对于野生型和各种突变体，蛋白2C表达为GST融合蛋白和His标记的蛋白。虽然有三个突变位于保守的NTP结合基序中或附近，但在HBB或胍的存在下，NTP活性没有改变。
HBB [2-(alpha-hydroxybenzyl)-benzimidazole] and guanidine are potent inhibitors of picornavirus replication. Among other evidence, limited cross-resistance and a synergistic effect of both inhibitors suggest similar but not identical mechanisms of antiviral action. Echovirus-9 variants resistant to each of these drugs were characterized and sequenced. Complete resistance to HBB or guanidine was shown to be due to single but different point mutations in the non-structural protein 2C. Protein 2C was expressed as GST fusion and His-tagged proteins for the wild-type and various mutants. Although three mutations were located in or near conserved NTP binding motifs, NTPase activity was not altered in the presence of HBB or guanidine.