Multivalency plays a central role in viral infection and bacterial adhesion, cell-cell communication, cancer metastasis, etc. Multivalent recognition relies on multiple weak individual interactions between the ligands and receptors resulting in collectively much stronger interactions than the corresponding monovalent connections. Moreover, the multivalent interactions are reversible and highly dynamic.<br/>The concept of multivalency was exploited in the design of new sensors and drugs to improve the existing diagnosis tools and treatment. For instance, the attachment of the influenza virus to the cell membrane is known to proceed through the interaction of the viral lectin hemagglutinin to the sialic acid epitopes on the cell surface. The development of new drugs with multivalent sialic acid representation capable to inhibit the virus-cell association is considered an alternative antiviral treatment.  However, the design of such drugs includes the synthesis of complex compounds such as dendrimers, polymers, and fullerenes ad require multistep organic synthesis. Moreover, the covalent ligand anchoring that prevents the ligand mobility and adaptability leads to a drop in their affinity and inhibition properties.<br/>Here we present a novel approach, reversible self-assembled monolayers (rSAMs), that allow to mimic the mobility of the cell membranes and to construct highly potent multivalent virus inhibitors. The formation of the rSAMs is driven by the spontaneous assembly of the benzamidine-terminated amphiphiles on alkanoic acid functionalized substrates (e.g. SAMs of thiols on gold) in a neutral or alkaline aqueous solution. We demonstrated that these scaffolds bearing the sialic acid head groups can interrupt pathogen-host cell interactions at pM range concentrations with no precedents to be found among previously reported glyconanomaterial-based inhibitors. Hence, we believe that rSAMs are an attractive tool for the design of multivalent inhibitors and new highly potent antiviral drug candidates.

Reversible self-assembled monolayers: Multivalent dynamic platform for detection, inhibition, differentiation of influenza virus

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