Coumarins and pyranocoumarins, potential novel pharmacophores for inhibition ofmeasles virus replication

ranks as one of the leading causes of infectious diseaseinduced morbidity and mortality in childhood throughout the world. Currently, 30–40 million measles infections occur worldwide each year leading to 1–2 million deaths (Manchester et al., 2000). In addition to causing an acute respiratory infection, this disease is also associated with a serious, but transient suppression of cell-mediated immunity (Wyde et al., 2000), apparently mediated by virus proteins resistant to heat treatment (Marttila et al., 2001). This immunosuppression can lead to secondary infections, and major complications such as pneumonia and diarrhoea in children, especially in those suffering from malnutrition (Griffin & Bellini, 1996). In rare cases, it can also cause encephalitis and persistent central nervous system infections (Griffin & Bellini, 1996). Although the use of a live attenuated virus has nearly eradicated the endemic circulation of measles in the USA and in other highly industrialized nations, re-introduction of the virus can still cause repeated limited outbreaks (Gay, 2000). In addition, vaccine safety has occasionally been questioned because of tenuous links to Crohn’s disease and particularly to autism (Kawashima et al., 2000). No studies to date, however, have conclusively established a causal relationship with vaccine viruses and those two diseases (Afzal et al., 2000). Therefore, campaigns need to be Antiviral Chemistry & Chemotherapy 13:39–59