期刊
NUCLEOSIDES NUCLEOTIDES & NUCLEIC ACIDS
卷 24, 期 10-12, 页码 1395-1415出版社
TAYLOR & FRANCIS INC
DOI: 10.1080/15257770500265638
关键词
S-adenosylhomocysteine (AdoHcy, SAH); adenosine analogues; carbocyclic adenosine analogues; acyclic adenosine analogues; carbocyclic 3-deazaadenosine (C-c(3) Ado); 3-deazaneplanocin A; poxviruses (vaccinia virus); hemorrhagic fever viruses (Ebola virus); rhabdoviruses (vesicular stomatitis virus); paramyxoviruses
Ever since the S-adenosylhomocysteine (AdoHcy, SAH) hydrolase was recognized as a pharmacological target for antiviral agents (J. A. Montgomery et al., J. Med. Chem. 25:626-629, 1982), an increasing number of adenosine, acyclic adenosine, and carbocyclic adenosine analogues have been described as potent SAH hydrolase inhibitors endowed with broad-spectrum antiviral activity. The antiviral activity spectrum of the SAH hydrolase inhibitors include pox-, rhabdo-, filo-, arena-, paramyxo-, reo-, and retroviruses. Among the most potent SAH hydrolase inhibitors and antiviral agents rank carbocyclic 3-deazaadenosine (C-c(3) Ado), neplanocin A, 3-deazaneplanocin A, the 5'-nor derivatives of carbocyclic adenosine (C-Ado, aristeromycin), and the 2-halo (i.e., 2-fluoro) and 6'- R -alkyl (i.e., 6' -R -methyl) derivatives of neplanocin A. These compounds are particularly active against poxviruses (i.e., vaccinia virus), and rhabdoviruses (i.e., vesicular stomatitis virus). The in vivo efficacy of C-c(3) Ado and 3-deazaneplanocin A has been established in mouse models for vaccinia virus, vesicular stomatitis virus, and Ebola virus. SAH hydrolase inhibitors such as C-c(3) Ado and 3-deazaneplanocin A should in the first place be considered for therapeutic (or prophylactic) use against poxvirus infections, including smallpox, and hemorrhagic fever virus infections such as Ebola.
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