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The hallmark of HSV is lifelong latent infections and viral reactivations, leading to recurrent lesions or asymptomatic shedding. HSV\u20101 and HSV\u20102 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\u2010threatening 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\u2010resistant HSV strains can emerge in relation to long\u2010term 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\u2010based 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.<\/jats:p>","DOI":"10.1002\/smmd.20220004","type":"journal-article","created":{"date-parts":[[2022,12,16]],"date-time":"2022-12-16T10:48:10Z","timestamp":1671187690000},"source":"Crossref","is-referenced-by-count":14,"title":["Current landscape in antiviral drug development against herpes simplex virus infections"],"prefix":"10.1002","volume":"1","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0394-5849","authenticated-orcid":false,"given":"Fanny","family":"Frejborg","sequence":"first","affiliation":[{"name":"Pharmaceutical Sciences Laboratory Faculty of Science and Engineering \u00c5bo Akademi University  Turku Finland"},{"name":"Institute of Biomedicine Faculty of Medicine University of Turku  Turku Finland"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kiira","family":"Kalke","sequence":"additional","affiliation":[{"name":"Institute of Biomedicine Faculty of Medicine University 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