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新型核苷类似物治疗出血热病毒感染。

New Nucleoside Analogues for the Treatment of Hemorrhagic Fever Virus Infections.

机构信息

Department of Microbiology, Immunology and Transplantation, Rega Institute for Medical Research, KU Leuven, Herestraat 49, 3000, Leuven, Belgium.

出版信息

Chem Asian J. 2019 Nov 18;14(22):3962-3968. doi: 10.1002/asia.201900841. Epub 2019 Aug 7.

Abstract

Eight different compounds, all nucleoside analogues, could presently be considered as potential drug candidates for the treatment of Ebola virus (EBOV) and/or other hemorrhagic fever virus (HFV) infections. They can be considered as either (i) adenine analogues (3-deazaneplanocin A, galidesivir, GS-6620 and remdesivir) or (ii) guanine analogues containing the carboxamide entity (ribavirin, EICAR, pyrazofurin and favipiravir). All eight owe their mechanism of action to hydrogen bonded base pairing with either (i) uracil or (ii) cytosine. Four out of the eight compounds (galidesivir, GS-6620, remdesivir and pyrazofurin) are C-nucleosides, and two of them (GS-6620, remdesivir) also contain a phosphoramidate part. The C-nucleoside and phosphoramidate (and for the adenine analogues the 1'-cyano group as well) may be considered as essential attributes for their antiviral activity.

摘要

目前,有八种不同的化合物,均为核苷类似物,可以被视为治疗埃博拉病毒(EBOV)和/或其他出血热病毒(HFV)感染的潜在候选药物。这些化合物可被分为两类:(i)腺嘌呤类似物(3-去氮杂环胞苷、加洛韦、GS-6620 和瑞德西韦)或(ii)含羧酰胺基的鸟嘌呤类似物(利巴韦林、EICAR、吡唑呋喃和法匹拉韦)。这八种化合物的作用机制均为通过氢键与尿嘧啶或胞嘧啶碱基配对。这八种化合物中有四种(加洛韦、GS-6620、瑞德西韦和吡唑呋喃)为 C-核苷,其中两种(GS-6620、瑞德西韦)还含有磷酰胺酯部分。C-核苷和磷酰胺酯(以及腺嘌呤类似物的 1'-氰基)可被视为其抗病毒活性的必要属性。

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