Fradet-Turcotte Amélie, Archambault Jacques
Laboratory of Molecular Virology, Institut de Recherches Cliniques de Montréal, Montreal, Quebec, Canada.
Antivir Ther. 2007;12(4):431-51.
Infection by human papillomavirus (HPV) is extremely common and associated with the development of benign warts or malignant lesions of the skin and mucosa. Infection by a high-risk (oncogenic) anogenital HPV type, most often through sexual contacts, is the starting point of virtually all cases of cervical cancers and the majority of anal cancers. The same viral types are also increasingly being linked with a subset of head-and-neck and non-melanoma skin cancers. Although prophylactic vaccines are now available to protect against the four types most commonly found in cervical and anal cancers (HPV16 and HPV18) and anogenital warts (HPV6 and HPV11), these neither protect against all genital HPVs nor are of therapeutic utility for already infected patients. Thus, the need for antiviral agents to treat HPV-associated diseases remains great, but none currently exist. This article reviews the recent progress made towards the development of antiviral agents to treat HPV infections, from target identification and validation to the discovery of lead compounds with therapeutic potential. Emphasis has been placed on novel low-molecular-weight compounds that antagonize HPV proteins or, alternatively, inhibit cellular proteins which have been usurped by papillomaviruses and are mediating their pathogenic effects.
人乳头瘤病毒（HPV）感染极为常见，与皮肤和黏膜的良性疣或恶性病变的发生有关。高危（致癌性）肛门生殖器HPV型感染，通常通过性接触传播，实际上是所有宫颈癌病例和大多数肛门癌病例的起始点。同样的病毒类型也越来越多地与一部分头颈癌和非黑色素瘤皮肤癌相关联。尽管现在有预防性疫苗可预防宫颈癌和肛门癌中最常见的四种类型（HPV16和HPV18）以及肛门生殖器疣（HPV6和HPV11），但这些疫苗既不能预防所有生殖器HPV感染，对已感染患者也没有治疗作用。因此，对抗病毒药物治疗HPV相关疾病的需求仍然很大，但目前尚无此类药物。本文综述了在开发治疗HPV感染的抗病毒药物方面取得的最新进展，从靶点识别与验证到具有治疗潜力的先导化合物的发现。重点关注了新型低分子量化合物，这些化合物可拮抗HPV蛋白，或者抑制被乳头瘤病毒篡夺并介导其致病作用的细胞蛋白。
