tetano
Editor, Senior Moderator
Nat Commun
. 2022 Nov 16;13(1):6716.
doi: 10.1038/s41467-022-34339-w.
XNAzymes targeting the SARS-CoV-2 genome inhibit viral infection
Pehuén Pereyra Gerber[SUP] 1 [/SUP], Maria J Donde[SUP] 1 [/SUP], Nicholas J Matheson[SUP] 1 2 3 [/SUP], Alexander I Taylor[SUP] 4 [/SUP]
Affiliations
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.
. 2022 Nov 16;13(1):6716.
doi: 10.1038/s41467-022-34339-w.
XNAzymes targeting the SARS-CoV-2 genome inhibit viral infection
Pehuén Pereyra Gerber[SUP] 1 [/SUP], Maria J Donde[SUP] 1 [/SUP], Nicholas J Matheson[SUP] 1 2 3 [/SUP], Alexander I Taylor[SUP] 4 [/SUP]
Affiliations
- PMID: 36385143
- DOI: 10.1038/s41467-022-34339-w
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.