Frejborg Fanny, Kalke Kiira, Hukkanen Veijo
Pharmaceutical Sciences Laboratory Faculty of Science and Engineering Åbo Akademi University Turku Finland.
Institute of Biomedicine Faculty of Medicine University of Turku Turku Finland.
Smart Med. 2022 Dec 16;1(1):e20220004. doi: 10.1002/SMMD.20220004. eCollection 2022 Dec.
Herpes simplex viruses (HSV) are common human pathogens with a combined global seroprevalence of 90% in the adult population. HSV-1 causes orofacial herpes but can cause severe diseases, such as the potentially fatal herpes encephalitis and herpes keratitis, a prevalent cause of infectious blindness. The hallmark of HSV is lifelong latent infections and viral reactivations, leading to recurrent lesions or asymptomatic shedding. HSV-1 and HSV-2 can cause recurrent, painful, and socially limiting genital lesions, which predispose to human immunodeficiency virus infections, and can lead to neonatal herpes infections, a life-threatening condition for the newborn. Despite massive efforts, there is no vaccine against HSV, as both viruses share the capability to evade the antiviral defenses of human and to establish lifelong latency. Recurrent and primary HSV infections are treated with nucleoside analogs, but the treatments do not completely eliminate viral shedding and transmission. Drug-resistant HSV strains can emerge in relation to long-term prophylactic treatment. Such strains are likely to be resistant to other chemotherapies, justifying the development of novel antiviral treatments. The importance of developing new therapies against HSV has been recognized by the World Health Organization. In this review, we discuss the current approaches for developing novel antiviral therapies against HSV, such as small molecule inhibitors, biopharmaceuticals, natural products, gene editing, and oligonucleotide-based therapies. These approaches may have potential in the future to answer the unmet medical need. Furthermore, novel approaches are presented for potential eradication of latent HSV.
单纯疱疹病毒（HSV）是常见的人类病原体，在全球成年人口中的综合血清阳性率为90%。HSV-1引起口腔面部疱疹，但也可导致严重疾病，如可能致命的疱疹性脑炎和疱疹性角膜炎，后者是传染性失明的常见原因。HSV的标志是终身潜伏感染和病毒再激活，导致复发性病变或无症状排毒。HSV-1和HSV-2可引起复发性、疼痛性且对社交有影响的生殖器病变，这些病变易引发人类免疫缺陷病毒感染，并可导致新生儿疱疹感染，这对新生儿来说是一种危及生命的状况。尽管付出了巨大努力，但目前尚无针对HSV的疫苗，因为这两种病毒都有能力逃避人类的抗病毒防御并建立终身潜伏感染。复发性和原发性HSV感染用核苷类似物治疗，但这些治疗不能完全消除病毒排毒和传播。长期预防性治疗可能会出现耐药HSV毒株。此类毒株可能对其他化疗药物耐药，这使得开发新型抗病毒治疗方法变得合理。世界卫生组织已经认识到开发针对HSV的新疗法的重要性。在本综述中，我们讨论了目前开发针对HSV的新型抗病毒疗法的方法，如小分子抑制剂、生物制药、天然产物、基因编辑和基于寡核苷酸的疗法。这些方法未来可能有潜力满足未满足的医疗需求。此外，还提出了潜在根除潜伏HSV的新方法。
