General-purpose virus-neutralizing engulfing shells with modular target-specificity

Viral infections affect millions of people every year and cause tremendous human suffering and costs to society. For approximately 70% of all WHO listed viruses, no treatment is available and the antiviral drugs that do exist typically must be applied very early after infection to be effective. The VIROFIGHT consortium proposes a radically new approach to fight viral infections, to help reduce the scale and sheer impact of viral infections, to address the problem of a lack of broadly applicable antiviral treatments, and to create means for combating emerging pathogens. Instead of targeting virus-specific proteins or enzymes by small molecules as current antivirals do, we will construct synthetic nano-shells that can specifically recognize and engulf entire viruses to efficiently neutralize the pathogen by occlusion. To achieve this technological target, our interdisciplinary project integrates supramolecular chemistry, molecular nanoengineering, and virology with the mission to develop and test prototypes of engulfing nano-shells that have the principal capacity to neutralize any given virus. We will fabricate biocompatible nano-shells through DNA origami and protein design and attach modularly virus-specific molecules to them in a multivalent fashion, to exploit avidity effects for strong virus binding. The virus binders will be identified through rapid in vitro selection processes designed to be applicable to any target virus. Neutralization assays will be used to test our concept on a variety of viruses. VIROFIGHT has the potential to attain revolutionary properties: shell prototypes can be developed and produced in the course of weeks after discovery of a viral pathogen, and the drug concept can be used and adapted for a wide variety of viral pathogens, without having detailed knowledge about the virus. The VIROFIGHT concept aimed at eradicating multiple viruses thus has great potential for decreasing the burden for patients and saving costs to society.