HIV protease inhibitor nelfinavir inhibits replication of SARS-associated coronavirus.

HIV protease inhibitor nelfinavir inhibits replication of SARS-associated coronavirus.
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DOI:
10.1016/j.bbrc.2004.04.083
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发表时间:
2004-06-04
影响因子:
3.1
通讯作者:
Yamamoto N
Yamamoto N
中科院分区:
生物学4区
文献类型:
--
作者:
Yamamoto N;Yang R;Yoshinaka Y;Amari S;Nakano T;Cinatl J;Rabenau H;Doerr HW;Hunsmann G;Otaka A;Tamamura H;Fujii N;Yamamoto N

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一种新型冠状病毒已被确定为严重急性呼吸综合征(SARS)的病原体。为了快速识别可用于临床的抗SARS药物,我们筛选了一组化合物,其中包括已经广泛使用的抗病毒药物。在此,我们报告 HIV-1 蛋白酶抑制剂奈非那韦可强烈抑制 SARS 冠状病毒 (SARS-CoV) 的复制。奈非那韦抑制 SARS-CoV 感染引起的细胞病变效应。用奈非那韦处理的感染细胞中病毒抗原的表达比未处理的感染细胞低得多。定量 RT-PCR 分析表明奈非那韦可以减少 Vero 细胞病毒颗粒的产生。不同药物添加时间的实验表明,奈非那韦不是在SARS-CoV感染的进入步骤中发挥作用,而是在进入后步骤中发挥作用。我们的研究结果表明,奈非那韦应该在治疗 SARS 方面进行临床检验,并且有潜力作为设计抗 SARS 药物的良好先导化合物。
A novel coronavirus has been identified as an etiological agent of severe acute respiratory syndrome (SARS). To rapidly identify anti-SARS drugs available for clinical use, we screened a set of compounds that included antiviral drugs already in wide use. Here we report that the HIV-1 protease inhibitor, nelfinavir, strongly inhibited replication of the SARS coronavirus (SARS-CoV). Nelfinavir inhibited the cytopathic effect induced by SARS-CoV infection. Expression of viral antigens was much lower in infected cells treated with nelfinavir than in untreated infected cells. Quantitative RT-PCR analysis showed that nelfinavir could decrease the production of virions from Vero cells. Experiments with various timings of drug addition revealed that nelfinavir exerted its effect not at the entry step, but at the post-entry step of SARS-CoV infection. Our results suggest that nelfinavir should be examined clinically for the treatment of SARS and has potential as a good lead compound for designing anti-SARS drugs.
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