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

Author

Listed:
  • Pehuén Pereyra Gerber

    (University of Cambridge)

  • Maria J. Donde

    (University of Cambridge)

  • Nicholas J. Matheson

    (University of Cambridge
    University of Cambridge
    NHS Blood and Transplant)

  • Alexander I. Taylor

    (University of Cambridge)

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.

Suggested Citation

  • Pehuén Pereyra Gerber & Maria J. Donde & Nicholas J. Matheson & Alexander I. Taylor, 2022. "XNAzymes targeting the SARS-CoV-2 genome inhibit viral infection," Nature Communications, Nature, vol. 13(1), pages 1-12, December.
    • Handle: RePEc:nat:natcom:v:13:y:2022:i:1:d:10.1038_s41467-022-34339-w
    DOI: 10.1038/s41467-022-34339-w
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    References listed on IDEAS

    as
    1. Changchang Cao & Zhaokui Cai & Xia Xiao & Jian Rao & Juan Chen & Naijing Hu & Minnan Yang & Xiaorui Xing & Yongle Wang & Manman Li & Bing Zhou & Xiangxi Wang & Jianwei Wang & Yuanchao Xue, 2021. "The architecture of the SARS-CoV-2 RNA genome inside virion," Nature Communications, Nature, vol. 12(1), pages 1-14, December.
    2. Alexander I. Taylor & Vitor B. Pinheiro & Matthew J. Smola & Alexey S. Morgunov & Sew Peak-Chew & Christopher Cozens & Kevin M. Weeks & Piet Herdewijn & Philipp Holliger, 2015. "Catalysts from synthetic genetic polymers," Nature, Nature, vol. 518(7539), pages 427-430, February.
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