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1-β-D-呋喃核糖基-1,2,4-三唑-3-甲酰胺(病毒唑,ICN 1229)对脱氧核糖核酸病毒和核糖核酸病毒的体外作用

In vitro effect of 1-beta-D-ribofuranosyl-1,2,4-triazole-3-carboxamide (virazole, ICN 1229) on deoxyribonucleic acid and ribonucleic acid viruses.

作者信息

Huffman J H, Sidwell R W, Khare G P, Witkowski J T, Allen L B, Robins R K

出版信息

Antimicrob Agents Chemother. 1973 Feb;3(2):235-41. doi: 10.1128/AAC.3.2.235.

Abstract

Virazole (1-beta-d-ribofuranosyl-1,2,4-triazole-3-carboxamide) is a highly soluble new synthetic nucleoside having significant, reproducible activity against a broad spectrum of deoxyribonucleic acid and ribonucleic acid viruses in vitro. The drug inhibited viral cytopathogenic effects in monolayers of cells infected for 3 days with type 3 adeno, types 1 and 2 herpes, myxoma, cytomegalo, vaccinia, infectious bovine rhinotracheitis, types 1A, 2, 8, 13, and 56 rhino, types 1 and 3 parainfluenza, vesicular stomatitis, subacute sclerosing panencephalitis, Semliki Forest, Newcastle disease, and measles viruses. Hemagglutinin production by influenza A(2), influenza B, and type 1 parainfluenza viruses in chicken embryo cells was reduced by Virazole treatment. Recoverable intra- and extracellular virus titers were reduced by the drug in experiments with type 1 herpes, vaccinia, type 3 parainfluenza, and vesicular stomatitis viruses. Plaque formation by type 1 herpesvirus was also inhibited by exposure of the infected cells to Virazole. Pretreatment of cells with the compound, followed by its removal before addition of type 1 herpesvirus, severely lessened the antiviral activity; the compound was still moderately effective in reducing the viral effects on the cells when added as long as 22 hr after the virus. Parallel experiments, in which the antiviral activity of a number of known active drugs was compared, indicated Virazole to have at least a comparable degree of activity, and it was also active against a wider variety of viruses than any of these known active materials. The CCED(50) of Virazole to chicken embryo cells was approximately 1,000 mug/ml, although concentrations as low as 10 mug/ml caused slight (15%) inhibition in total cellular protein after 72 hr of incubation.

摘要

病毒唑(1-β-D-呋喃核糖基-1,2,4-三唑-3-甲酰胺)是一种高度可溶的新型合成核苷,在体外对多种脱氧核糖核酸和核糖核酸病毒具有显著的、可重复的活性。该药物抑制了在单层细胞中感染3天的3型腺病毒、1型和2型疱疹病毒、黏液瘤病毒、巨细胞病毒、痘苗病毒、传染性牛鼻气管炎病毒、1A、2、8、13和56型鼻病毒、1型和3型副流感病毒、水疱性口炎病毒、亚急性硬化性全脑炎病毒、塞姆利基森林病毒、新城疫病毒和麻疹病毒所产生的病毒致细胞病变效应。用病毒唑处理可降低甲型流感病毒(2型)、乙型流感病毒和1型副流感病毒在鸡胚细胞中血凝素的产生。在1型疱疹病毒、痘苗病毒、3型副流感病毒和水疱性口炎病毒的实验中,该药物降低了可恢复的细胞内和细胞外病毒滴度。将感染细胞暴露于病毒唑也可抑制1型疱疹病毒形成蚀斑。用该化合物对细胞进行预处理,然后在加入1型疱疹病毒之前将其去除,会严重降低抗病毒活性;当在病毒加入后长达22小时添加该化合物时,它在降低病毒对细胞的影响方面仍有一定效果。在一些平行实验中,比较了多种已知活性药物的抗病毒活性,结果表明病毒唑至少具有相当程度的活性,而且它比任何一种已知活性物质对更多种类的病毒都有活性。病毒唑对鸡胚细胞的CCED(50)约为1000μg/ml,尽管在孵育72小时后,低至10μg/ml的浓度会导致总细胞蛋白有轻微(15%)的抑制。

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