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

Published version
Peer-reviewed

Type

Article

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Authors

Pereyra Gerber, Pehuen 
Matheson, Nicholas J  ORCID logo  https://orcid.org/0000-0002-3318-1851
Taylor, Alexander I  ORCID logo  https://orcid.org/0000-0001-7684-1437

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--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.

Description

Keywords

Journal Title

Nature Communications

Conference Name

Journal ISSN

2041-1723
2041-1723

Volume Title

Publisher

Nature Research
Sponsorship
Wellcome Trust (215453/Z/19/Z)
Collaborator Nicholas Matheson is supported by: MRC (TSF ref. MR/T032413/1) NHSBT (grant ref. WPA15-02) The Addenbrooke’s Charitable Trust (grant ref. 900239) NIHR Cambridge BRC.