Additional file 1: Electronic Supplementary Material. 2009 Canada novel Influenza A(H1N1) daily laboratory-confirmed pandemic H1N1 case and hospitalization data. Antiviral and Neuroprotective Role of Octaguanidinium Dendrimer-Conjugated Morpholino Oligomers in Japanese Encephalitis BACKGROUND: Japanese encephalitis (JE), caused by a mosquito-borne flavivirus, is endemic to the entire south-east Asian and adjoining regions. Currently no therapeutic interventions are available for JE, thereby making it one of the most dreaded encephalitides in the world. An effective way to counter the virus would be to inhibit viral replication by using anti-sense molecules directed against the viral genome. Octaguanidinium dendrimer-conjugated Morpholino (or Vivo-Morpholino) are uncharged anti-sense oligomers that can enter cells of living organisms by endocytosis and subsequently escape from endosomes into the cytosol/nuclear compartment of cells. We hypothesize that Vivo-Morpholinos generated against specific regions of 3′ or 5′ untranslated regions of JEV genome, when administered in an experimental model of JE, will have significant antiviral and neuroprotective effect. METHODOLOGY/PRINCIPAL FINDINGS: Mice were infected with JEV (GP78 strain) followed by intraperitoneal administration of Morpholinos (5 mg/kg body weight) daily for up to five treatments. Survivability of the animals was monitored for 15 days (or until death) following which they were sacrificed and their brains were processed either for immunohistochemical staining or protein extraction. Plaque assay and immunoblot analysis performed from brain homogenates showed reduced viral load and viral protein expression, resulting in greater survival of infected animals. Neuroprotective effect was observed by thionin staining of brain sections. Cytokine bead array showed reduction in the levels of proinflammatory cytokines in brain following Morpholino treatment, which were elevated after infection. This corresponded to reduced microglial activation in brain. Oxidative stress was reduced and certain stress-related signaling molecules were found to be positively modulated following Morpholino treatment. In vitro studies also showed that there was decrease in infective viral particle production following Morpholino treatment. CONCLUSIONS/SIGNIFICANCE: Administration of Vivo-Morpholino effectively resulted in increased survival of animals and neuroprotection in a murine model of JE. Hence, these oligomers represent a potential antiviral agent that merits further evaluation. The genus Flavivirus is composed of more than 70 different closely related species [1] . Many flaviviruses are arthropod-borne and causes significant human diseases. Among these, the four serotypes of dengue virus (DENV), yellow fever virus (YFV), West Nile virus (WNV) and Japanese encephalitis virus (JEV) are categorized as emerging global pathogens [2] . JEV is a mosquitoborne, positive sense, single stranded RNA virus, responsible for frequent epidemics of encephalitis, predominantly in children, in most parts of Southeast Asia and adjoining regions. It is the causal factor for 30,000-50,000 cases of encephalitis occurring every year and accounts for about 10,000 deaths annually with serious neurological squeal in the survivors [3] . JEV has been expanding its 'geographical footprint' into previously non-endemic regions and with several billion people at risk, Japanese encephalitis (JE) represents an internationally emerging concern in tropical and sub-tropical countries. Currently three types of JE vaccine are in use-the inactivated mouse-brain derived, the inactivated cellculture derived and the live attenuated cell-culture derived. However, there are limitations for their usage in terms of availability, cost and safety [4] . At present, chemotherapy against JEV is largely supportive and not targeted towards the virus. A lot of avenues has been explored in the past and are also being currently tried, so as to develop a safe and effective molecule that would be able to prevent the virus from replicating within the host.