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Breaking the Resistance Barrier: A Mini-Review of the Advancements in Second-Line Treatments for HSV-1, HSV-2 and VZV Infections

Kimberly C Lince, Virgil K De Mario, Rachel Pittman, Rebecca L Sanchez

This mini-review aims to evaluate a systematic review of the available literature on the efficacy of second-line treatments for Herpes Simplex Viruses (HSV) that are resistant to first-line antiviral agents. The systematic review included a search of six databases for eligible manuscripts using terms related to antiviral resistance, herpes, and HSV. A total of 137 articles were included in qualitative synthesis, examining the relationship between viral resistance to first-line treatments and potential second-line treatments in HSV. Of the included studies, 84.67% reported on HSV-1, with 34.31% of these studies reporting testing on resistant HSV strains. The following interventions were found to be effective as potential managements for resistant strains of HSV: nectin, amenamevir, methanol extract, monoclonal antibodies, arbidol, siRNA swarms, cucumis melo sulfated pectin, components from oleano europeae, griffithsin, morus alba L., nucleosides, botryosphaeran, monoterpenes, almond skin extracts, bortezomib, and flavonoid compounds. The available literature reviewed consistently supported the existence and potentiality of second-line treatments for HSV strains that are resistant to first-line treatments. Therefore, the review provided necessary information about treatment options for patients with resistant HSV infections, particularly those who are immunocompromised, and their providers.