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香港和美國(guó)科學(xué)家聯(lián)合宣布，他們找到了一種能夠有效抑制流感病毒、包括H5N1禽流感病毒繁殖的化合物，研究發(fā)表在最新一期的《藥物化學(xué)雜志》（JMC）上。 研究人員對(duì)美國(guó)國(guó)立癌癥研究所登記的23萬(wàn)種化合物進(jìn)行了仔細(xì)篩選。他們發(fā)現(xiàn)，其中的20種化合物能夠抑制H5N1型病毒的繁殖。專家稱，其中名為“化合物—1號(hào)”、代號(hào)為NSC89853的一種化合物有望抑制流感病毒的繁殖。 在實(shí)驗(yàn)中，研究人員使用了季節(jié)性流感病毒和H5N1型病毒感染培養(yǎng)的人類(lèi)細(xì)胞，結(jié)果表明，NSC89853號(hào)化合物能夠有效抑制這兩種病毒的繁殖。香港大學(xué)的微生物專家潘烈文（音譯）說(shuō)，這種化合物與奧司他偉（藥物名為“達(dá)菲”）不同，但作用一樣。 許多發(fā)達(dá)國(guó)家都使用奧司他偉和扎拉米韋來(lái)對(duì)抗H5N1禽流感病毒的繁殖，但今年3月份，美國(guó)疾病控制和預(yù)防中心發(fā)表報(bào)告稱，所有的H1N1菌種流感樣本都對(duì)奧司他偉產(chǎn)生了抗藥性。因此，找到新的病毒“抑制劑”變得日益緊迫。專家目前正在研究這種化合物對(duì)H5N1型病毒的藥效時(shí)間及效用。 推薦原始出處： J. Med. Chem.,DOI: 10.1021/jm800455g A Novel Small-Molecule Inhibitor of the Avian Influenza H5N1 Virus Determined through Computational Screening against the Neuraminidase Jianghong An, Davy C. W. Lee, Anna H.Y. Law, Cindy L.H. Yang, Leo L.M. Poon, Allan S.Y. Lau* and Steven J.M. Jones* British Columbia Cancer Agency Genome Sciences Centre, 675 West 10th Avenue, Vancouver, British Columbia V5Z 4S6, Canada, Cytokine Biology Group, Department of Paediatrics and Adolescent Medicine, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, Special Administrative Region, China, and Department of Microbiology, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Pokfulam, Hong Kong, Special Administrative Region, China Computational molecular docking provides an efficient and innovative approach to examine small molecule and protein interactions. We have utilized this method to identify potential inhibitors of the H5N1 neuraminidase protein. Of the 20 compounds tested, 4-(4-((3-(2-amino-4-hydroxy-6-methyl-5-pyrimidinyl)propyl)amino)phenyl)-1-chloro-3-buten-2-one (1) (NSC89853) demonstrated the ability to inhibit viral replication at a level comparable to the known neuraminidase inhibitor oseltamivir. Compound 1 demonstrated efficacy across a number of cell-lines assays and in both the H1N1 and H5N1 viruses. The predicted binding of 1 to the known H5N1 neuraminidase structure indicates a binding interface largely nonoverlapping with that of oseltamivir or another neuraminidase inhibitor zanamivir. These results indicate that 1 or similar molecules would remain effective in the presence of virus mutations conferring resistance to either oseltamivir or zanamivir and also vice versa. (責(zé)任編輯：Doctor001) |
