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Existing anti\u2010HSV therapies are not completely successful in eliminating the infection due to anti\u2010viral drug resistance, ineffectiveness against the latent virus and high toxicity over prolonged use. There is a need to update our knowledge of the current challenges faced in anti\u2010HSV therapeutics and realize the necessity of developing alternative treatment approaches. Protein therapeutics are now being explored as a novel approach due to their high specificity and low toxicity. This review highlights the significance of HSV viral glycoproteins and host receptors in the pathogenesis of HSV infection. Proteins or peptides derived from HSV glycoproteins gC, gB, gD, gH and host cell receptors (HSPG, nectin and HVEM) that act as decoys to inhibit HSV attachment, entry, or fusion have been discussed. Few researchers have tried to improve the efficacy and stability of the identified peptides by modifying them using a peptidomimetic approach. With these efforts, we think developing an alternative treatment option for immunocompromised patients and drug\u2010resistant organisms is not far off.<\/jats:p>","DOI":"10.1111\/1751-7915.14342","type":"journal-article","created":{"date-parts":[[2023,9,23]],"date-time":"2023-09-23T07:40:34Z","timestamp":1695454834000},"page":"2036-2052","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":7,"title":["A critical review on antiviral peptides derived from viral glycoproteins and host receptors to decoy herpes simplex virus"],"prefix":"10.1111","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-2105-7551","authenticated-orcid":false,"given":"Rakesh","family":"Rahangdale","sequence":"first","affiliation":[{"name":"Department of Pharmaceutical Biotechnology, Manipal College of Pharmaceutical Sciences Manipal Academy of Higher Education  Manipal Karnataka 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