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While DENV infection manifests with a spectrum of clinical symptoms, severe cases can lead to hemorrhagic fever and shock syndrome. Increasing evidence over the past decade has highlighted the neurological complications associated with DENV; however, the underlying mechanisms remain poorly understood. Despite this knowledge gap, various central nervous system (CNS)\u2013targeted drugs have shown promise in mitigating DENV\u2010induced neurological impairment. In this review, we provide an overview of the neurotropic features of DENV and summarize current evidence on the antiviral effects of selected nervous system\u2010acting compounds. We also explore the potential mechanisms by which these agents may reduce DENV infection. Given the urgent need for effective dengue therapeutics, repurposing CNS\u2010targeting drugs represents a promising strategy. 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