Abstract
Dengue virus represents a global public health threat, being prevalent in tropical and subtropical regions, with an increasing geographical distribution and rising incidence worldwide. This mosquito-borne viral agent causes a wide range of clinical manifestations, from mild febrile illness to severe cases and potentially fatal outcomes due to hemorrhage and shock syndrome. The etiological agent, dengue virus (DENV), has four distinct serotypes, each capable of inducing severe clinical outcomes. The current therapeutic landscape remains limited, with management strategies mainly focused on supportive cares. However, recent advances in pharmaceutical research have yielded promising developments in anti-dengue drugs. Extensive investigations have been conducted on various synthetic compounds, including JNJ-1802, 1,4-pyran naphthoquinones, and arylnaphthalene lignan derivatives. Additionally, natural compounds derived from medicinal plants such as Hippophae rhamnoides, Azadirachta indica, and Cymbopogon citratus have demonstrated potential antiviral properties in both in vitro and in vivo studies, based on inhibition of DENV replication. However, none of these compounds are to date approved by the U.S. Food and Drug Administration (FDA). Although many vaccines have been recognized as candidates in various stages of clinical trials, only a limited number of these have demonstrated a protective efficacy against the infection. This aspect underscores the need for both highly effective immunization strategies and therapeutic interventions, whether derived from botanical sources or through synthetic manufacturing, that exhibit low adverse effects. This review examines innovative approaches to DENV prevention and treatment, encompassing both phytochemical and synthetic therapeutic strategies.