Reverse engineering synthetic antiviral amyloids

• Published in: Nature communications Vol. 11; no. 1; pp. 2832 - 13
• Main Authors: Michiels, Emiel, Roose, Kenny, Gallardo, Rodrigo, Khodaparast, Ladan, Khodaparast, Laleh, van der Kant, Rob, Siemons, Maxime, Houben, Bert, Ramakers, Meine, Wilkinson, Hannah, Guerreiro, Patricia, Louros, Nikolaos, Kaptein, Suzanne J F, Ibañez, Lorena Itatí, Smet, Anouk, Baatsen, Pieter, Liu, Shu, Vorberg, Ina, Bormans, Guy, Neyts, Johan, Saelens, Xavier, Rousseau, Frederic, Schymkowitz, Joost
• Format: Journal Article
• Language: English
• Published: England Nature Publishing Group 05.06.2020; Nature Publishing Group UK; Nature Portfolio
• Subjects: Amyloid - genetics; Amyloid - pharmacology; Amyloid - therapeutic use; Animals; Antiviral Agents - pharmacology; Antiviral Agents - therapeutic use; Chemical compounds; Disease Models, Animal; Dogs; Drug development; Female; HEK293 Cells; Homology; Host-Pathogen Interactions - drug effects; Humans; Influenza; Influenza A; Influenza A virus - drug effects; Influenza A virus - genetics; Influenza A virus - pathogenicity; Influenza B; Influenza, Human - drug therapy; Influenza, Human - virology; Madin Darby Canine Kidney Cells; Mice; Pharmacology; Polymorphism, Genetic; Proteins; Recombinant Proteins - genetics; Recombinant Proteins - pharmacology; Recombinant Proteins - therapeutic use; Replication; Reverse engineering; Reverse Genetics - methods; Synthetic Biology - methods; Vector-borne diseases; Viral Proteins - genetics; Viral Proteins - metabolism; Virus Replication - drug effects; Viruses; Zika virus; Zika Virus - drug effects; Zika Virus - genetics; Zika Virus - pathogenicity; Zika Virus Infection - drug therapy; Zika Virus Infection - virology
• ISSN: 2041-1723; 2041-1723
• DOI: 10.1038/s41467-020-16721-8

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.