Bifunctional polymeric inhibitors of human influenza A viruses.
Bifunctional polymeric inhibitors of human influenza A viruses.
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DOI：
10.1007/s11095-009-0013-1
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发表时间：
2010-02
影响因子：
3.7
通讯作者：
Klibanov, Alexander M.
中科院分区：
文献类型：
--
作者：
Haldar, Jayanta;de Cienfuegos, Luis Alvarez;Tumpey, Terrence M.;Gubareva, Larisa V.;Chen, Jianzhu;Klibanov, Alexander M.
将唾液酸(1)和扎那米韦(2)的衍生物与聚（异丁烯-马来酸酐）（聚-(1+2)）或聚-1和聚-2混合，制备了新的抗病毒药物，并对野生型和耐药甲型流感武汉病毒进行了测定。1和2分别或一起以共价键与聚合物结合。使用斑块减少试验评估所得poly-1、poly-2、poly-(1+2)和poly-1 + poly-2以及1和2的抗病毒效力。将1附着在聚合物上，在最好的情况下提高了三个数量级以上的毫摩尔IC50值。2的IC50值为微摩尔，poly-2的IC50值为100倍。poly-(1+2)对野生型菌株的IC50分别比poly-1和poly-2高300倍和17倍。相比之下，poly-(1+2)和poly-2对突变株的效力仅增加了一倍。poly-1 + poly-2的混合物对两种病毒株的抑制作用类似于poly-2。与单功能poly-1和poly-2的物理混合物相比，双功能poly-(1+2)对野生型流感病毒起协同作用，但对其耐药突变体不起作用。
New antiviral agents were prepared by attaching derivatives of sialic acid (1) and of the drug zanamivir (2) to poly(isobutylene-alt-maleic anhydride) (poly-(1+2)) or by mixing poly-1 and poly-2, followed by assaying them against wild-type and drug-resistant influenza A Wuhan viruses. Individually or together, 1 and 2 were covalently bonded to the polymer. The antiviral potencies of the resultant poly-1, poly-2, poly-(1+2), and poly-1 + poly-2, as well as 1 and 2, were assessed using plaque reduction assay. Attaching 1 to the polymer improved at best millimolar IC50 values over three orders of magnitude. While 2 exhibited micromolar IC50 values, poly-2 was >100-fold even more potent. The IC50 of poly-(1+2) against the wild-type strain was >300-fold and ~17-fold better than of poly-1 and poly-2, respectively. In contrast, the potency of poly-(1+2) vs. poly-2 against the mutant strain merely doubled. The mixture of poly-1 + poly-2 inhibited both viral strains similarly to poly-2. The bifunctional poly-(1+2) acts synergistically against the wild-type influenza virus, but not against its drug-resistant mutant, as compared to a physical mixture of the monofunctional poly-1 and poly-2.
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影响因子：
1.7
作者：
Masuda, T;Yoshida, S;Honda, T
通讯作者：
Honda, T
影响因子：
11.8
作者：
Dowdle, WR
通讯作者：
Dowdle, WR
DOI：
10.1038/nrd2175
发表时间：
2006-12
期刊：
Nature reviews. Drug discovery
影响因子：
--
作者：
De Clercq E
通讯作者：
De Clercq E
影响因子：
4.9
作者：
HAYDEN, FG;COTE, KM;DOUGLAS, RG
通讯作者：
DOUGLAS, RG
影响因子：
4.9
作者：
Yen, HL;Herlocher, LM;Govorkova, EA
通讯作者：
Govorkova, EA