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新型抗病毒药物研发亮点。

Highlights in the development of new antiviral agents.

作者信息

De Clercq E

机构信息

Rega Institute for Medical Research, Katholieke Universiteit Leuven, Leuven, B-3000, Belgium.

出版信息

Mini Rev Med Chem. 2002 Apr;2(2):163-75. doi: 10.2174/1389557024605474.

Abstract

The potential of a large variety of new compounds and new strategies for the treatment of virtually all major virus infections has been addressed. This includes, for the treatment of HIV infections, virus adsorption inhibitors (cosalane derivatives, cyanovirin-N), co-receptor antagonists (TAK-779, AMD3100), viral fusion inhibitors (pentafuside T-20, betulinic acid derivatives), viral uncoating inhibitors (azodicarbonamide), nucleoside/nucleotide reverse transcriptase inhibitors (NRTIs: emtricitabine, amdoxovir, dOTC, d4TMP prodrugs, tenofovir disoproxil fumarate), non-nucleoside reverse transcriptase inhibitors (NNRTIs: thiocarboxanilide UC-781, capravirine, SJ-3366, DPC 083, TMC 125/R165335), integrase inhibitors (diketo acids), transcription inhibitors (temacrazine, flavopiridol), protease inhibitors (atazanavir, mozenavir, tipranavir); for the treatment of RSV and paramyxovirus infections, viral fusion inhibitors (R170591, VP-14637, NMS03); for the treatment of picornavirus infections, viral uncoating inhibitors (pleconaril); for the treatment of pesti- (hepaci-, flavi-) virus infections, RNA replicase inhibitors (VP-32947); for the treatment of herpesvirus (HSV, VZV, CMV) infections, DNA polymerase inhibitors (A-5021, L- and D-cyclohexenylguanine); for the treatment of VZV infections, bicyclic furopyrimidine analogues; for the treatment of CMV infections, fomivirsen; for the treatment of DNA virus infections at large (papilloma-, polyoma-, herpes-, adeno- and poxvirus infections), cidofovir; for the treatment of influenza, neuraminidase inhibitors (zanamivir, oseltamivir, RWJ-270201); for the treatment of HBV infections, adefovir dipivoxil; for the treatment of HBV and HCV infections, N-glycosylation inhibitors (N-nonyl-deoxynojirimycin); and, finally, IMP dehydrogenase inhibitors and S-adenosylhomocysteine hydrolase inhibitors, for the treatment of various virus infections, including hemorrhagic fever virus infections.

摘要

人们已经探讨了各种各样新化合物和新策略在治疗几乎所有主要病毒感染方面的潜力。这包括用于治疗HIV感染的病毒吸附抑制剂(考沙兰衍生物、氰胍蛋白-N)、共受体拮抗剂(TAK-779、AMD3100)、病毒融合抑制剂(喷他呋定T-20、桦木酸衍生物)、病毒脱壳抑制剂(偶氮二甲酰胺)、核苷/核苷酸逆转录酶抑制剂(NRTIs:恩曲他滨、氨多索韦、dOTC、d4TMP前药、替诺福韦酯)、非核苷逆转录酶抑制剂(NNRTIs:硫代羧酰苯胺UC-781、卡普瑞韦、SJ-3366、DPC 083、TMC 125/R165335)、整合酶抑制剂(二酮酸)、转录抑制剂(替马卡嗪、黄酮哌啶醇)、蛋白酶抑制剂(阿扎那韦、莫扎那韦、替拉那韦);用于治疗呼吸道合胞病毒和副粘病毒感染的病毒融合抑制剂(R170591、VP-14637、NMS03);用于治疗小RNA病毒感染的病毒脱壳抑制剂(普来可那立);用于治疗瘟病毒(肝炎病毒、黄病毒)感染的RNA复制酶抑制剂(VP-32947);用于治疗疱疹病毒(单纯疱疹病毒、水痘带状疱疹病毒、巨细胞病毒)感染的DNA聚合酶抑制剂(A-5021、L-和D-环己烯基鸟嘌呤);用于治疗水痘带状疱疹病毒感染的双环呋喃嘧啶类似物;用于治疗巨细胞病毒感染的福米韦生;用于治疗一般DNA病毒感染(乳头瘤病毒、多瘤病毒、疱疹病毒、腺病毒和痘病毒感染)的西多福韦;用于治疗流感的神经氨酸酶抑制剂(扎那米韦、奥司他韦、RWJ-270201);用于治疗乙肝感染的阿德福韦酯;用于治疗乙肝和丙肝感染的N-糖基化抑制剂(N-壬基-脱氧野尻霉素);最后还有肌苷酸脱氢酶抑制剂和S-腺苷同型半胱氨酸水解酶抑制剂,用于治疗包括出血热病毒感染在内的各种病毒感染。

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