Viruses belonging to the Flaviviridae family primarily spread through arthropod 
vectors, and are the major causes of illness and death around the globe. The 
Flaviviridae family consists of 3 genera which include the Flavivirus genus 
(type species, yellow fever virus) as the largest genus, the Hepacivirus (type 
species, hepatitis C virus) and the Pestivirus (type species, bovine virus 
diarrhea). The flaviviruses (Flavivirus genus) are small RNA viruses transmitted 
by mosquitoes and ticks that take over host cell machinery in order to 
propagate. However, hepaciviruses and pestiviruses are not antropod-borne. 
Despite the extensive research and public health concern associated with 
flavivirus diseases, to date, there is no specific treatment available for any 
flavivirus infections, though commercially available vaccines for yellow fever, 
Japanese encephalitis and tick-born encephalitis exist. Due to the global threat 
of viral pandemics, there is an urgent need for new drugs. In many countries, 
patients with severe cases of flavivirus infections are treated only by 
supportive care, which includes intravenous fluids, hospitalization, respiratory 
support, and prevention of secondary infections. This review discusses the 
strategies used towards the discovery of antiviral drugs, focusing on rational 
drug design against Dengue virus (DENV), West Nile virus (WNV), Japanese 
encephalitis virus (JEV), Yellow Fever virus (YFV) and Hepatitis C virus (HCV). 
Only modified peptidic, nonpeptidic, natural compounds and fragment-based 
inhibitors (typically of mass less than 300 Da) against structural and 
non-structural proteins are discussed.