BackgroundJapanese encephalitis virus (JEV) is a major cause of viral encephalitis in South and South-East Asia. Lack of antivirals and non-availability of affordable vaccines in these endemic areas are a major setback in combating JEV and other closely related viruses such as West Nile virus and dengue virus. Protein secondary structure mimetics are excellent candidates for inhibiting the protein-protein interactions and therefore serve as an attractive tool in drug development. We synthesized derivatives containing the backbone of naturally occurring lupin alkaloid, sparteine, which act as protein secondary structure mimetics and show that these compounds exhibit antiviral properties.Methodology/Principal FindingsIn this study we have identified 3,7-diazabicyclo[3.3.1]nonane, commonly called bispidine, as a privileged scaffold to synthesize effective antiviral agents. We have synthesized derivatives of bispidine conjugated with amino acids and found that hydrophobic amino acid residues showed antiviral properties against JEV. We identified a tryptophan derivative, Bisp-W, which at 5 µM concentration inhibited JEV infection in neuroblastoma cells by more than 100-fold. Viral inhibition was at a stage post-entry and prior to viral protein translation possibly at viral RNA replication. We show that similar concentration of Bisp-W was capable of inhibiting viral infection of two other encephalitic viruses namely, West Nile virus and Chandipura virus.Conclusions/SignificanceWe have demonstrated that the amino-acid conjugates of 3,7-diazabicyclo[3.3.1]nonane can serve as a molecular scaffold for development of potent antivirals against encephalitic viruses. Our findings will provide a novel platform to develop effective inhibitors of JEV and perhaps other RNA viruses causing encephalitis.

A series of designer lipidated pseudopeptidic triazolophanes was synthesized using a copper-catalyzed azide-alkyne cycloaddition reaction. These 32-membered cyclophanes form sturdy vesicles and pot-like supramolecular structures, as demonstrated by ultramicroscopic studies.

We designed and synthesized bispidine-anchored peptides and showed that these peptides as small as (containing four chiral α-amino acid residues) adopt a right handed helical conformation. Bispidine anchored linear peptide adopts a helical conformation in solution and in the solid state.

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Through various examples, we demonstrated serine as an excellent building block for the design of chiral and non-chiral self-assembled materials. The fine parameters such as pitch, angle and helicity can be altered using clever molecular engineering.