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Dengue is the most prevalent arthropod-borne viral disease worldwide and affects approximately 2.5 billion people living in over 100 countries. Increasing geographic expansion of Aedes aegypti mosquitoes (which transmit the virus) has made dengue a global health concern. There are currently no approved antivirals available to treat dengue, and the only approved vaccine used in some countries is limited to seropositive patients. Treatment of dengue, therefore, remains largely supportive to date; hence, research efforts are being intensified for the development of antivirals. The nonstructural proteins, 3 and 5 (NS3 and NS5), have been the major targets for dengue antiviral development due to their indispensable enzymatic and biological functions in the viral replication process. NS5 is the largest and most conserved nonstructural protein encoded by flaviviruses. Its multifunctionality makes it an attractive target for antiviral development, but research efforts have, this far, not resulted in the successful development of an antiviral targeting NS5. Increase in structural insights into the dengue NS5 protein will accelerate drug discovery efforts focused on NS5 as an antiviral target. In this review, we will give an overview of the current state of therapeutic development, with a focus on NS5 as a therapeutic target against dengue.

Dengue is a major public health problem in hyperendemic countries like Colombia,the understanding of the epidemiological trends is important for the development of efficientpublic health policies. We conducted a systematic review of the epidemiologic data on dengue inColombia from 1971 to 2020. A total of 375 relevant citations were identified, 36 of which fulfilled theinclusion criteria. The data of dengue and severe dengue cases, infection fatality rate, and serotypedistribution were used to understand and identify gaps in the epidemiological knowledge in Colombia.The epidemiology of dengue in this country was characterized by five main outbreaks in 1998, 2002,2010, 2013, and 2019 with high fatality rates in comparison with the average values reported in theAmericas. The case fatality rate of severe dengue exceeded 2% and all four serotypes co-circulatethroughout the country with some regional variations. Overall, the behavior of dengue in Colombia isinfluenced by multiple factors including seasonal temperature variation and socioeconomic conditions.Additionally, the most important barriers in the epidemiological surveillance of dengue may be dueto the insufficient notification rate in some regions and the low active search for the circulation ofdifferent serotypes.