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香港和美国科学家联合宣布，他们找到了一种能够有效抑制流感病毒、包括H5N1禽流感病毒繁殖的化合物，研究发表在最新一期的《药物化学杂志》（JMC）上。 研究人员对美国国立癌症研究所登记的23万种化合物进行了仔细筛选。他们发现，其中的20种化合物能够抑制H5N1型病毒的繁殖。专家称，其中名为“化合物—1号”、代号为NSC89853的一种化合物有望抑制流感病毒的繁殖。 在实验中，研究人员使用了季节性流感病毒和H5N1型病毒感染培养的人类细胞，结果表明，NSC89853号化合物能够有效抑制这两种病毒的繁殖。香港大学的微生物专家潘烈文（音译）说，这种化合物与奥司他伟（药物名为“达菲”）不同，但作用一样。 许多发达国家都使用奥司他伟和扎拉米韦来对抗H5N1禽流感病毒的繁殖，但今年3月份，美国疾病控制和预防中心发表报告称，所有的H1N1菌种流感样本都对奥司他伟产生了抗药性。因此，找到新的病毒“抑制剂”变得日益紧迫。专家目前正在研究这种化合物对H5N1型病毒的药效时间及效用。 推荐原始出处： 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. (责任编辑：Doctor001) |
