BackgroundAutism Spectrum Disorder (ASD) is a complex neurobehavioral syndrome with no known biomarker so far for early detection. It has been challenging, both to classify typical autism and associate a suitable biomarker with clinical phenotype spectrum. Brain-derived neurotrophic factor (BDNF) has emerged as a key neurotrophin regulating synaptic plasticity, neuronal differentiation and survival.PurposeRecently, BDNF depletion is reported in neurodegenerative as well as in psychiatric disorders, associated with severity of neurological dysfunction. Role of BDNF as a biomarker in ASD is gaining significance. Pre-clinical results have linked BDNF depletion in autism and mental retardation, however, with conflicting findings.MethodsIn view of this, a preliminary study was carried out to measure serum BDNF levels in 48 children with ASD and mental retardation, and 29 age-matched controls.ResultsSerum BDNF levels were found significantly higher (p<0.001) in atypical autistic subjects (clinically milder phenotype) as compared to controls, but not in typical ASD cases (clinically severe phenotype). BDNF levels were significantly lower in females with typical/Rett Syndrome (p<0.05), but not in males with typical autism (p>0.1), as compared to controls. Lower BDNF levels indicate impairment in neuroprotective mechanism, while higher levels may imply a manifested protective response.ConclusionOur study highlights the differential BDNF response based on the severity of neurobehavioral deficit, indicating a possible neuroprotective role of this molecule and supporting its exploration in targeted therapy in ASD.

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Influenza is a serious respiratory illness which can be debilitating and cause complications that lead to hospitalization and death. Although influenza vaccine can prevent influenza virus infection, the only therapeutic options to treat influenza virus infection are antiviral agents. Given temporal and geographic changes and the shifts in antiviral drug resistance among influenza viruses, it is time to consider natural antiviral agents against influenza virus. Jatropha curcas is known for various medicinal uses. Its antimicrobial, anti-cancer and anti-HIV activity has been well recognized. Because of its broadspectrum activity, we investigated aqueous and methanol leaf extracts for cytotoxicity and its potential to inhibit hemagglutinin protein of influenza virus. The bioactive compounds from leaf extracts were characterized by highperformance thinlayer chromatography which revealed the presence of major phytochemicals including flavonoids, saponins and tannins. The cytotoxic concentration 50 for aqueous and methanol extracts were determined using trypan blue dye exclusion assay. Inhibition of hemagglutinin protein was assessed using minimal cytotoxic concentrations of the extracts and 10 2.5 TCID50 (64 HA titre) of the Influenza A (H1N1) virus with different exposure studies using hemagglutination assay. Aqueous and methanol extracts were found to be non toxic to Madin darby canine kidney cells below concentration of 15.57 and 33.62 mg/mL for respectively. Inhibition of hemagglutinin was studied using reducing hemagglutination titre which confirmed that the J. curcas extracts have direct effect on the process of virus adsorption leading to its inhibition. Our results provide the information which shows the potential of Jatropha extracts in the treatment of influenza A (H1N1) virus infection. With an established reduced toxicity and prevention of infection by inhibiting hemagglutinin protein, these extracts and its derivatives may be further developed as broad spectrum anti-influenza drugs for prevention and treatment of infections by different types of influenza viruses with further mechanistic studies on antiinfluenza.

Considering the need for discovery of new antiviral drugs, in view to combat the issue of resistance particularly to anti-influenza drugs, a series of 2'-amino, 3'-amino and 2', 4'-dihydroxy chalcone derivatives were designed. Structure-based drug design was used to design inhibitors of influenza virus - H1N1 neuraminidase enzyme. These were further optimized by a combination of iterative medicinal chemistry principles and molecular docking. Based on the best docking scores, some chalcone derivatives were synthesized and characterized by infrared spectroscopy (IR) and proton nuclear magnetic resonance (NMR). The molecules were evaluated for their anti-influenza action against influenza A/Pune isolate/2009 (H1N1) virus by in vitro enzyme-based assay (neuraminidase inhibition assay). We have then selected few of them for multinuclear NMR studies, 31P NMR, in order to probe the molecular mechanism of their antiviral action. Reasonably good correlation between docking scores; anti-influenza activity; and 31P NMR results were observed. The computational predictions were in consensus with the experimental results. It was observed that among tested compounds, derivative 1A, viz. 2', 4'-dihydroxy-4-methoxy chalcone, showed highest activity (IC50 = 2.23 μmol/l) against the virus under study. This derivative 1A can be explored further to provide a future therapeutic option for the treatment and prophylaxis of H1N1 viral infections.

We conclude that non-competitive type of inhibition, as shown in this study, can serve as an effective method to block NA and evade the currently seen drug resistance.