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XNAzymes targeting the SARS-CoV-2 genome inhibit viral infection. | LitMetric

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

Nat Commun

Cambridge Institute of Therapeutic Immunology & Infectious Disease (CITIID), Jeffrey Cheah Biomedical Centre, University of Cambridge, Cambridge, UK.

Published: November 2022

AI Article Synopsis

Article 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.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC9668987PMC
http://dx.doi.org/10.1038/s41467-022-34339-wDOI Listing

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