Multivalent Supramolecular Nanosystems as Dynamic Virus Blockers

Background: Viral pandemics pose great risks to current and future human health and global trade. Newly emerging viruses can display a broad variety of shapes, such as spherical or filamentous, and spike proteins have different lengths and densities, as seen in coronaviruses and influenza viruses. Viruses can mutate rapidly under evolutionary pressure, resulting in changes to antigen epitopes and reduced efficacy of drugs and vaccines. These variances between viruses and across mutations present challenges to broad-based anti-infection intervention and vaccination. However, the initial docking of viruses to cell surface receptors via heparan sulfate or polysialic acids are common for a number of viruses, offering an attractive target for wide-reaching intervention. Aim: The SupraVir project will provide a new concept for multivalent supramolecular assemblies as self-adaptive universal virus blockers. This new type of virus inhibitor can adapt to different virus morphologies and mutations by dynamic self-assembly of its virus binding sites. The inhibitor will use a combination of different receptors and bind a great majority of all known viruses by mimicking generic host cell surface receptors. Methodology: My approach will use self-assembled surface-active supramolecules that mimic the host cell surface efficiently and dynamically. With this method I will avoid a bulk phase that does not contribute to the activity, thus reducing potential toxicity. At the same time, the amphiphilic building blocks can interfere with the viral envelope or capsid and permanently inactivate the virus. Impact: SupraVir addresses the central question: What might prevention of viral infections look like in 2030? I contend that there is a new option, based on mimicking dynamic cell surface receptors with multivalent supramolecular nanosystems that can self-adapt to inactivate rapidly mutating viruses.