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利巴韦林、5-乙炔基-1-β-D-呋喃核糖基咪唑-4-甲酰胺和6'-(R)-6'-C-甲基新制癌菌素A对几种正黏病毒和副黏病毒的抗病毒活性。

Antiviral activities of ribavirin, 5-ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide, and 6'-(R)-6'-C-methylneplanocin A against several ortho- and paramyxoviruses.

作者信息

Shigeta S, Mori S, Baba M, Ito M, Honzumi K, Nakamura K, Oshitani H, Numazaki Y, Matsuda A, Obara T

机构信息

Department of Bacteriology, Fukushima Medical College, Japan.

出版信息

Antimicrob Agents Chemother. 1992 Feb;36(2):435-9. doi: 10.1128/AAC.36.2.435.

Abstract

5-Ethynyl-1-beta-D-ribofuranosylimidazole-4-carboxamide (EICAR) and 6'-(R)-6'-C-methylneplanocin A (TJ13025) are two novel antiviral agents which are targeted against IMP dehydrogenase and S-adenosylhomocysteine hydrolase, respectively. These compounds have been examined for their activities against various strains of orthomyxoviruses (influenza virus) and paramyxoviruses (parainfluenza virus, mumps virus, measles virus, and respiratory syncytial virus) in vitro. EICAR was 10- to 59-fold more active than ribavirin and TJ13025 was 32- to 330-fold more active than ribavirin against parainfluenza virus types (2 and 3), mumps virus, and measles virus. EICAR was also more active than ribavirin against respiratory syncytial virus and influenza virus, whereas TJ13025 was virtually inactive against these viruses. The 50% virus-inhibitory concentrations of EICAR and TJ13025 were generally within the 0.1- to 1-microgram/ml range. Although the compounds did not prove cytotoxic to stationary host cells (HeLa, Vero, MDCK, and LLCMK2) at a concentration of 200 micrograms/ml, concentrations of 4 to 13 micrograms/ml inhibited the growth of dividing cells. EICAR and TJ13025 should be further pursued as candidate drugs for the treatment of ortho- and paramyxovirus infections.

摘要

5-乙炔基-1-β-D-呋喃核糖基咪唑-4-甲酰胺(EICAR)和6'-(R)-6'-C-甲基新渥霉素A(TJ13025)是两种新型抗病毒药物,分别作用于肌苷酸脱氢酶和S-腺苷同型半胱氨酸水解酶。已对这些化合物在体外针对各种正粘病毒株(流感病毒)和副粘病毒株(副流感病毒、腮腺炎病毒、麻疹病毒和呼吸道合胞病毒)的活性进行了检测。在针对副流感病毒2型和3型、腮腺炎病毒及麻疹病毒时,EICAR的活性比利巴韦林高10至59倍,TJ13025的活性比利巴韦林高32至330倍。EICAR对呼吸道合胞病毒和流感病毒的活性也高于利巴韦林,而TJ13025对这些病毒几乎无活性。EICAR和TJ13025的50%病毒抑制浓度一般在0.1至1微克/毫升范围内。尽管在200微克/毫升浓度下这些化合物对静止的宿主细胞(HeLa、Vero、MDCK和LLCMK2)未显示出细胞毒性,但4至13微克/毫升的浓度会抑制分裂细胞的生长。EICAR和TJ13025应作为治疗正粘病毒和副粘病毒感染的候选药物进一步研究。

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