Activity of Selected Amaryllidaceae Constituents and Related Synthetic Substances Against Medically Important RNA Viruses

RNA viruses comprising the families, Togaviridae, Bunyaviridae, Arenaviridae and Filoviridae cause hemorrhagic, encephalitic or febrile disease and represent significant health hazards to persons living in or traveling through endemic regions of the world. These viruses include: a) Japanese encephalitis (JE), yellow fever (YF) and dengue type 1–4 viruses (flaviviruses); b) Rift Valley fever (RVF), sandfly fever (Sicilian, SF), Hantaan (hemorrhagic fever with renal syndrome, HFRS) and Crimean-Congo hemorrhagic fever (CCHF) viruses (bunyaviruses); c) Venezuelan equine encephalitis virus (VEE, alphavirus); d) Lassa (LAS) and Junin (JUN) viruses (arenaviruses); and e) Ebola (EBO) and Marburg (MAR) viruses (filoviruses). In general, these viruses are associated with insect (mosquito, tick) or rodent vectors, occur primarily in Asia, Africa or Central/South America, may require an increased level of biohazard protection, and are often referred to as “exotic” viruses in the context of “tropical” medicine (Figure 1). These diseases occur world-wide but the development of appropriate antiviral chemotherapies is not considered economically feasible by the private sector. The drug discovery program of the U.S. Army Medical Research Institute of Infectious Diseases (USAMRIID) seeks to develop antiviral chemotherapeutic agents against several of these viruses. This task is hampered by a limited knowledge of many of the diseases and viruses, the remote location of disease outbreaks with the inherent problems in conducting clinical studies and the requirement for BL3 and BL4 (“spacesuit”) laboratories for biocontainment.