Pyrc Krzysztof, Bosch Berend Jan, Berkhout Ben, Jebbink Maarten F, Dijkman Ronald, Rottier Peter, van der Hoek Lia
Department of Human Retrovirology, University of Amsterdam, The Netherlands.
Antimicrob Agents Chemother. 2006 Jun;50(6):2000-8. doi: 10.1128/AAC.01598-05.
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 RNA1 (siRNA1), siRNA2, beta-D-N(4)-hydroxycytidine, and 6-azauridine showed 50% inhibitory concentrations of 125 microg/ml, 2 microM, 5 nM, 3 nM, 400 nM, and 32 nM, respectively, and low 50% cytotoxicity concentrations (>10 mg/ml, >40 microM, >200 nM, >200 nM, >100 microM, and 80 microM, respectively). These agents may be investigated further for the treatment of coronavirus infections.
人冠状病毒NL63（HCoV-NL63）是冠状病毒科最近发现的成员，已在全球传播，与幼儿、老年人及免疫功能低下者的急性呼吸道疾病有关。似乎有必要对HCoV-NL63的致病性进行进一步分析，特别是因为该病毒与严重急性呼吸综合征相关冠状病毒使用相同的细胞受体。由于目前尚无针对HCoV-NL63的特异性有效疫苗或药物疗法，我们评估了几种现有抗病毒药物和新合成化合物作为HCoV-NL63的抑制剂，它们作用于病毒复制周期的多个阶段。在我们测试的28种化合物中，有6种在复制周期早期有效抑制了HCoV-NL63。静脉注射免疫球蛋白、七肽重复序列2肽、小干扰RNA1（siRNA1）、siRNA2、β-D-N(4)-羟基胞苷和6-氮杂尿苷的50%抑制浓度分别为125μg/ml、2μM、5 nM、3 nM、400 nM和32 nM，且50%细胞毒性浓度较低（分别>10 mg/ml、>40μM、>200 nM、>200 nM、>100μM和80μM）。这些药物可进一步研究用于治疗冠状病毒感染。
