Development of antiviral agents toward enterovirus 71 infection

Enterovirus 71 (EV71) is a pathogenic serotype of the Picornaviridae family, containing a single positive sense RNA genome with a length of approximately 7.5 kb. Detected during a small outbreak in California between 1969 and 1972,1 EV71 has now been turned into one of the most pathogenic Enterovirus serotypes with many outbreaks occurring around the world, particularly in the Asia-Pacific region. Although EV71 infection usually manifests with rashes and vesicular lesions on the hands, feet, and oral mucosa,2 it sometimes leads to fatal neurological complications such as aseptic meningitis, encephalitis, acute respiratory disease, and pulmonary edema.3 Following the large outbreaks in both Malaysia and Taiwan in the late 1990s,4 new life-threatening outbreaks of EV71 reoccurred in Taiwan in 2001–20025 and in China in 2010.6 There is no approved vaccine or antiviral drug available for prophylaxis or treatment of EV71 infection to date.7 Therefore, research studies should continue to develop novel EV71 inhibitors and as such, latest achievements in this field always have to be updated. At least three recent reviews have detailed a range of studies undertaken in both fields of EV71: antivirals and vaccines.7–9 However, compared to EV71 vaccine development, a large number of research ventures conducted into EV71 antiviral development has generated vast information on novel compounds with anti-EV71 capacity and even improved the understanding of EV71–host interactions. Hence, this review attempts to provide a focused body of information regarding the status and challenges of antiviral therapy for EV71, covering both options: synthetic and natural bioactive compounds. In addition, we discuss how newly discovered EV71 cellular receptors might lead to new avenues for anti-EV71 drug design.