[en] Emerging and re-emerging RNA viruses continue to challenge global health preparedness, underscoring the need for broad-spectrum antivirals that can be rapidly deployed. We propose a family-specific antiviral design strategy that targets conserved replication-transcription complexes (RTCs) using nanobodies delivered as mRNA therapeutics. This approach overcomes the long-standing limitation of intracellular delivery of antibody-based biologics. By expressing antiviral nanobodies directly inside infected cells via lipid-nanoparticle-encapsulated mRNA, it becomes possible to disrupt essential protein-protein interactions within viral RTCs. Using SARS-CoV-2 non-structural protein 9 (NSP9) as a proof-of-concept, we show that stabilizing non-functional NSP9 oligomers can inhibit viral replication. This combined nanobody-mRNA technology provides a versatile platform for rapid antiviral development across virus families.
Blavier, Jeremy ; Université de Liège - ULiège > Département GxABT > Microbial technologies
Esposito, Gennaro; Division of Science and Mathematics, Biology Program, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates, Center for Genomics and Systems Biology (CGSB), New York University Abu Dhabi, Abu Dhabi, United Arab Emirates
Percipalle, Piergiorgio; Division of Science and Mathematics, Biology Program, New York University Abu Dhabi, Abu Dhabi, United Arab Emirates, Center for Genomics and Systems Biology (CGSB), New York University Abu Dhabi, Abu Dhabi, United Arab Emirates. Electronic address: pp69@nyu.edu
Language :
English
Title :
Targeting viral replication complexes with mRNA-encoded nanobodies: a new frontier for antiviral design.
NYU Abu Dhabi - New York University Abu Dhabi F.R.S.-FNRS - Fonds de la Recherche Scientifique
Funding text :
We thank Adeline Deward, Illuminesciences (Belgium), for help with the illustrations and Valentina Fambri for critically reading the manuscript. This work was supported by grants from New York University Abu Dhabi and by Tamkeen under the NYU Abu Dhabi Research Institute Award to the NYUAD Center for Genomics and Systems Biology (ADHPG-CGSB) to PP. J-C.T. is a Senior Investigator of the Fonds de la Recherche Scientifique (FRS-FNRS, Belgium). J.B. is a fellow of Les Amis des Instituts Pasteur \u00E0 Bruxelles. P.P. and J-C.T. conceived the perspective idea and wrote the manuscript together with G.E. and J.B.
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