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XNAzymes targeting the SARS-CoV-2 genome inhibit viral infection

Pehuén Pereyra Gerber, Maria J. Donde, Nicholas J. Matheson and Alexander I. Taylor ()
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Pehuén Pereyra Gerber: University of Cambridge
Maria J. Donde: University of Cambridge
Nicholas J. Matheson: University of Cambridge
Alexander I. Taylor: University of Cambridge

Nature Communications, 2022, vol. 13, issue 1, 1-12

Abstract: Abstract The unprecedented emergence and spread of SARS-CoV-2, the coronavirus responsible for the COVID-19 pandemic, underscores the need for diagnostic and therapeutic technologies that can be rapidly tailored to novel threats. Here, we show that site-specific RNA endonuclease XNAzymes – artificial catalysts composed of single-stranded synthetic xeno-nucleic acid oligonucleotides (in this case 2’-deoxy-2’-fluoro-β-D-arabino nucleic acid) – may be designed, synthesised and screened within days, enabling the discovery of a range of enzymes targeting SARS-CoV-2 ORF1ab, ORF7b, spike- and nucleocapsid-encoding RNA. Three of these are further engineered to self-assemble into a catalytic nanostructure with enhanced biostability. This XNA nanostructure is capable of cleaving genomic SARS-CoV-2 RNA under physiological conditions, and when transfected into cells inhibits infection with authentic SARS-CoV-2 virus by RNA knockdown. These results demonstrate the potential of XNAzymes to provide a platform for the rapid generation of antiviral reagents.

Date: 2022
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DOI: 10.1038/s41467-022-34339-w

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