Inhibition of human coronavirus NL63 infection at early stages of the replication cycle
Inhibition of human coronavirus NL63 infection at early stages of the replication cycle
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DOI：
10.1128/aac.01598-05
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发表时间：
2006-06-01
影响因子：
4.9
通讯作者：
van der Hoek, Lia
中科院分区：
文献类型：
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作者：
Pyrc, Krzysztof;Bosch, Berend Jan;van der Hoek, Lia
人冠状病毒NL 63（HCoV-NL 63）是冠状病毒科（Coronaviridae）的一个新发现的成员，已在全球范围内传播，并与幼儿、老年人和免疫功能低下者的急性呼吸道疾病有关。对HCoV-NL 63致病性的进一步分析似乎是必要的，特别是因为该病毒使用与严重急性呼吸综合征相关冠状病毒相同的细胞受体。由于目前没有HCoV-NL 63特异性和有效的疫苗或药物治疗，我们评估了几种现有的抗病毒药物和新的合成化合物作为HCoV-NL 63的抑制剂，靶向复制周期的多个阶段。在我们测试的28种化合物中，有6种在复制周期的早期阶段有效抑制HCoV-NL 63。静脉内免疫球蛋白、七肽重复序列2肽、小干扰RNAi（siRNA 1）、siRNA 2、β-D-N-4-羟基胞苷和6-氮杂尿苷分别显示出125 μ g/ml、2 μ M、5 nM、3 nM、400 nM和32 nM的50%抑制浓度和低50%细胞毒性浓度（分别> 10 mg/ml、> 40 μ M、> 200 nM、> 200 nM、> 100 μ M和80 μ M）。可以进一步研究这些药物用于治疗冠状病毒感染。
Human coronavirus NL63 (HCoV-NL63), a recently discovered member of the Coronaviridae family, has spread worldwide and is associated with acute respiratory illness in young children and elderly and immunocompromised persons. Further analysis of HCoV-NL63 pathogenicity seems warranted, in particular because the virus uses the same cellular receptor as severe acute respiratory syndrome-associated coronavirus. As there is currently no HCoV-NL63- specific and effective vaccine or drug therapy available, we evaluated several existing antiviral drugs and new synthetic compounds as inhibitors of HCoV-NL63, targeting multiple stages of the replication cycle. Of the 28 compounds that we tested, 6 potently inhibited HCoV-NL63 at early steps of the replication cycle. Intravenous immunoglobulins, heptad repeat 2 peptide, small interfering RNAI (siRNA1), siRNA2, beta-D-N-4-hydroxycytidine, and 6-azauridine showed 50% inhibitory concentrations of 125 mu g/ml, 2 mu M, 5 nM, 3 nM, 400 nM, and 32 nM, respectively, and low 50% cytotoxicity concentrations (> 10 mg/ml, > 40 mu M, > 200 nM, > 200 nM, > 100 mu M, and 80 mu M, respectively). These agents may be investigated further for the treatment of coronavirus infections.