Research Projects

Despite significant advances in the vaccination or antiviral drug, treatment of viral infections continues to remain a major challenge, especially due to the emergence of new mutants and drug resistance. Stopping virus entry into host cells during initial infection is a promising approach for antiviral therapy. In this context, antiviral polymers have been studied with great interest, but they are mostly limited to natural sulfated poly-saccharides, apart from a very few recent examples exploring other structures. To expand the scope of synthetic materials in the treatment of viral diseases, this project aims to explore H-bonding driven directional supramolecular assembly of sulfated amphiphilic π-systems and polymers for developing new antiviral materials. Sulfate groups will be specifically employed as it interacts with the envelope spike composed of gp120 A and facilitates fusion of the virus particle with synthetic targets. In the first part, naphthalene diimide (NDI) derived unsymmetrical bola-shape π-amphiphiles will be studied, in which the central NDI core will be functionalized with a hydrophilic wedge and sulfate group(s) in the opposite arms. Single H-bonding group (hydrazide) will be placed selectively in one arm to ensure parallel orientation in the H-boding driven supramolecular polymerization, which eventually may lead to polymersome structure considering the shape of the amphiphiles. Direction of curvature may be regulated by the H-bonding chain, which in turn will allow to place the sulfate groups either in the outer or inner surface of the membrane. Further, morphology of the self-assembled structures will be tuned (polymersome, micelle, cylindrical structure) by varying the H-bonding functional group and the impact of surface functional group (sulfate) display and/ or shape of the nanostructures will be tested for antiviral activity using non-pathogenic Sendai virus. In the second part, new sulfated amphiphilic polymers will be tested in which the hydrophobic backbone will be segmented by H-bonding functional groups (urethane, amide or urea). Such polymers may significantly differ from the commonly seen immiscibility driven aggregation of amphiphilic copolymers due to the possibility of adopting folded structures by intra-chain H-bonding. Such intra-chain folding regulated hierarchical assembly will be studied as a function of the H-bonding group, and detail of their hierarchical assembly producing nanostructures with different shape (polymersome, cylindrical micelle or nanotube) will be investigated. Finally, the intrinsic primary structure of these polymers (hydrophobic/ hydrophilic balance, density of the pendant functional group (sulfate) and the nature of the H-bonding group, degree of polymerization etc.) as well as their chain-folding regulated self-assembled tertiary structures will be correlated with their antiviral activity.