Abstract 2667 Drugging NSP14: The Proofreader and Cap Builder of SARS-CoV-2's Genetic Blueprint
NSP14 is a dual-function enzyme which plays a key role in SARS-CoV-2 replication. Its C-terminal 3` to 5` exonuclease (ExoN) domain is important for proofreading nascent RNA. At the N-terminus the methyltransferase (MTase) domain performs the N7-methylation of the forming RNA cap, promoting stability of the genome and aiding in host evasion. Curiously, these domains function independently. Additionally, the ExoN activity depends on an accessory protein, NSP10 while the MTase domain is not. Both activities are enticing drug development targets.
Authors
- Quinlin Hanson (ORCID: https://orcid.org/0000-0001-6033-8415)
- Kelli M. Wilson (ORCID: https://orcid.org/0000-0003-2636-2766)
- Sourav Pal (ORCID: https://orcid.org/0000-0002-9120-8127)
- Katlin Recabo
- Alexey Zakharov (ORCID: https://orcid.org/0000-0003-2466-1711)
- Lin Ye (ORCID: https://orcid.org/0000-0003-0062-6436)
- Xin Hu (ORCID: https://orcid.org/0000-0003-1164-5130)
- Natalia Martínez (ORCID: https://orcid.org/0000-0002-7088-5751)
- Min Shen
Institutions
- National Center for Advancing Translational Sciences (US)
Publication Details
- Journal
- Journal of Biological Chemistry
- Published
- 2025-05-01
- DOI
- https://doi.org/10.1016/j.jbc.2025.109079
- Primary Topic
- interferon and immune responses
- Type
- article
- Field-Weighted Citation Impact
- 0.00