Andrei G, Topalis D, De Schutter T, Snoeck R
Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven, Belgium.
Laboratory of Virology and Chemotherapy, Department of Microbiology and Immunology, Rega Institute for Medical Research, KU Leuven, Belgium.
Antiviral Res. 2015 Feb;114:21-46. doi: 10.1016/j.antiviral.2014.10.012. Epub 2014 Oct 30.
Acyclic nucleoside phosphonates (ANPs) are well-known for their antiviral properties, three of them being approved for the treatment of human immunodeficiency virus infection (tenofovir), chronic hepatitis B (tenofovir and adefovir) or human cytomegalovirus retinitis (cidofovir). In addition, cidofovir is mostly used off-label for the treatment of infections caused by several DNA viruses other than cytomegalovirus, including papilloma- and polyomaviruses, which do not encode their own DNA polymerases. There is considerable interest in understanding why cidofovir is effective against these small DNA tumor viruses. Considering that papilloma- and polyomaviruses cause diseases associated either with productive infection (characterized by high production of infectious virus) or transformation (where only a limited number of viral proteins are expressed without synthesis of viral particles), it can be envisaged that cidofovir may act as antiviral and/or antiproliferative agent. The aim of this review is to discuss the advances in recent years in understanding the mode of action of ANPs as antiproliferative agents, given the fact that current data suggest that their use can be extended to the treatment of non-viral related malignancies.
无环核苷膦酸盐（ANPs）以其抗病毒特性而闻名，其中三种已被批准用于治疗人类免疫缺陷病毒感染（替诺福韦）、慢性乙型肝炎（替诺福韦和阿德福韦）或人类巨细胞病毒视网膜炎（西多福韦）。此外，西多福韦大多用于非适应症治疗，用于治疗由除巨细胞病毒外的几种DNA病毒引起的感染，包括乳头瘤病毒和多瘤病毒，这些病毒不编码自身的DNA聚合酶。人们对了解西多福韦为何对这些小型DNA肿瘤病毒有效有着浓厚的兴趣。鉴于乳头瘤病毒和多瘤病毒会引发与生产性感染（以高产量的感染性病毒为特征）或转化（仅表达有限数量的病毒蛋白而不合成病毒颗粒）相关的疾病，可以设想西多福韦可能作为抗病毒和/或抗增殖剂发挥作用。鉴于目前的数据表明ANPs的应用可以扩展到治疗非病毒相关的恶性肿瘤，本综述的目的是讨论近年来在理解ANPs作为抗增殖剂的作用方式方面取得的进展。
