Application of real-time PCR for testing antiviral compounds against Lassa virus, SARS coronavirus and Ebola virus in vitro.

Application of real-time PCR for testing antiviral compounds against Lassa virus, SARS coronavirus and Ebola virus in vitro.
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DOI:
10.1016/j.antiviral.2004.05.001
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发表时间:
2004-09
期刊:
影响因子:
7.6
通讯作者:
Hosmane RS
Hosmane RS
中科院分区:
医学2区
文献类型:
--
作者:
Günther S;Asper M;Röser C;Luna LK;Drosten C;Becker-Ziaja B;Borowski P;Chen HM;Hosmane RS

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本报告描述了实时PCR在检测抗高致病性病毒如拉沙病毒、SARS冠状病毒和埃博拉病毒的抗病毒药物中的应用。该检测结合了经典细胞培养和定量实时PCR读数。用利巴韦林验证了拉沙病毒的测定法,其显示IC 50为9 μg/ml。小规模筛选确定了一类具有抗拉沙病毒活性的咪唑核苷/核苷酸类似物。类似物在咪唑4,5-位含有二腈或二酯基团,并且其中许多在咪唑1-位具有无环糖或糖膦酸酯部分。最具活性化合物的IC 50值范围为5 - 21 μg/ml。这些化合物在类似的试验中也抑制了SARS冠状病毒和埃博拉病毒的复制,尽管程度低于拉沙病毒。
This report describes the application of real-time PCR for testing antivirals against highly pathogenic viruses such as Lassa virus, SARS coronavirus and Ebola virus. The test combines classical cell culture with a quantitative real-time PCR read-out. The assay for Lassa virus was validated with ribavirin, which showed an IC50 of 9 μg/ml. Small-scale screening identified a class of imidazole nucleoside/nucleotide analogues with antiviral activity against Lassa virus. The analogues contained either dinitrile or diester groups at the imidazole 4,5-positions, and many of which possessed an acyclic sugar or sugar phosphonate moiety at the imidazole 1-position. The IC50 values of the most active compounds ranged from 5 to 21 μg/ml. The compounds also inhibited replication of SARS coronavirus and Ebola virus in analogous assays, although to a lesser extent than Lassa virus.
DOI: 10.1056/nejm198601023140104
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