人巨细胞病毒抑制剂的研究进展

Research progress of human cytomegalovirus inhibitors

人巨细胞病毒(human cytomegalovirus,HCMV)是β疱疹病毒亚科的成员,是已知最大的人类病毒之一。HCMV在全球范围内广泛传播,在人群中血清阳性率为40%~100%。HCMV对免疫功能正常的个体影响较小,多数感染者无临床症状,但在免疫功能低下或缺陷的个体中,可引起严重的并发症,导致多器官衰竭甚至危及生命。目前尚无预防HCMV感染的有效疫苗,已批准的抗病毒药物(如更昔洛韦、缬更昔洛韦、膦甲酸、西多福韦和莱特莫韦)是唯一可行的抗HCMV方法。但在临床使用中,因为这些药物存在口服生物利用率低、抗病毒活性中等和耐药性等特点,极大限制了其临床治疗效用,亟需研发新的HCMV抑制剂。HCMV包含多种自身编码的蛋白质和不完全确定数量的宿主细胞蛋白质,这些蛋白质在其复制过程中发挥着重要的作用。本文从靶向病毒蛋白和宿主蛋白两个方面,对处于临床试验阶段的抑制剂和正在研究的新型抑制剂进行综述,为HCMV疾病治疗和药物研发提供一定的理论基础。

Human cytomegalovirus(HCMV)is a member of theβherpesvirus subfamily,which is one of the largest human viruses.HCMV is widely spread in the world,and the seropositive rate in the population is between 40%and 100%.HCMV has little effect on individuals with normal immune function,and most infected individuals have no clinical symptoms.However,in individuals with low or defective immune function,it can cause serious complications,leading to multiple organ failure and even life-threatening.There is no effective vaccine against HCMV infection,and approved antiviral drugs(such as ganciclovir,valganciclovir,foscarnet,cidofovir,and lete⁃movir)are the only methods available.But in clinical use,these drugs are characterized by low oral bioavailability,moderate antiviral activity and drug resistance,which greatly limit their clinical therapeutic utility.So the develop⁃ment of new HCMV inhibitors is urgently needed.HCMV contains a variety of self encoded proteins and an uncer⁃tain number of host cell proteins,which play an important role in its replication process.In this paper,we will re⁃view the inhibitors in clinical trials and new inhibitors under research from two aspects of targeting viral proteins and host proteins,so as to provide a theoretical basis for the treatment of HCMV disease and drug development.