Reverse engineering synthetic antiviral amyloids
Emiel Michiels, Kenny Roose, Rodrigo Gallardo, Ladan Khodaparast, Laleh Khodaparast, Rob van der Kant, Maxime Siemons, Bert Houben, Meine Ramakers, Hannah Wilkinson, Patrícia Guerreiro, Nikolaos Louros, Suzanne J. F. Kaptein, Lorena Itatí Ibañez, Anouk Smet, Pieter Baatsen, Shu Liu, Ina Vorberg, Guy Bormans, Johan Neyts, Xavier Saelens, Frédéric Rousseau, Joost Schymkowitz
Abstract
Human amyloids have been shown to interact with viruses and interfere with viral replication. Based on this observation, we employed a synthetic biology approach in which we engineered virus-specific amyloids against influenza A and Zika proteins. Each amyloid shares a homologous aggregation-prone fragment with a specific viral target protein. For influenza we demonstrate that a designer amyloid against PB2 accumulates in influenza A-infected tissue in vivo. Moreover, this amyloid acts specifically against influenza A and its common PB2 polymorphisms, but not influenza B, which lacks the homologous fragment. Our model amyloid demonstrates that the sequence specificity of amyloid interactions has the capacity to tune amyloid-virus interactions while allowing for the flexibility to maintain activity on evolutionary diverging variants.