title: Current approaches in antiviral drug discovery against the Flaviviridae family.
abstract: 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.
authors.forename: Aida
authors.initials: A
authors.lastname: Baharuddin
authors.forename: Asfarina Amir
authors.initials: AA
authors.lastname: Hassan
authors.forename: Gan Chye
authors.initials: GC
authors.lastname: Sheng
authors.forename: Shah Bakhtiar
authors.initials: SB
authors.lastname: Nasir
authors.forename: Shatrah
authors.initials: S
authors.lastname: Othman
authors.forename: Rohana
authors.initials: R
authors.lastname: Yusof
authors.forename: Rozana
authors.initials: R
authors.lastname: Othman
authors.affiliation: Department of Chemistry, Faculty of Science, University of Malaya, 50603 Kuala Lumpur, Malaysia. noorsaadah@um.edu.my.
authors.forename: Noorsaadah Abdul
authors.initials: NA
authors.lastname: Rahman
mesh_terms: D000998:Antiviral Agents / Q000494:pharmacology* / Q000627:therapeutic use; D015195:Drug Design; D055808:Drug Discovery / Q000379:methods*; D018067:Flaviviridae / Q000187:drug effects* / Q000201:enzymology; D018178:Flaviviridae Infections / Q000188:drug therapy; D006801:Humans; D058990:Molecular Targeted Therapy / Q000379:methods; D014764:Viral Proteins / Q000037:antagonists & inhibitors
chemical_list: D000998:Antiviral Agents; D014764:Viral Proteins