Insights from deep mutational scanning in the context of an emerging pathogen
- Details
- Publication Year 2025-10-29,Volume 53,Issue #5,Page 1169-1179
- Journal Title
- Biochemical Society Transactions
- Abstract
- Deep mutational scanning (DMS), a high-throughput method leveraging next-generation sequencing, has been crucial in mapping the functional landscapes of key severe acquired respiratory syndrome-coronavirus 2 (SARS-CoV-2) proteins. By systematically assessing thousands of amino acid changes, DMS provides a framework to understand Angiotensin-converting enzyme 2 (ACE2) binding and immune evasion by the spike protein, mechanisms and drug escape potential of the main and papain-like viral proteases and has highlighted areas of concern in the nucleocapsid protein that may affect most currently available rapid antigen testing kits. Each application has required the design of bespoke assays in eukaryotic (yeast and mammalian) cell models, providing an exemplar for the application of this technique to future pandemics. This minireview examines how DMS has predicted key evolutionary changes in SARS-CoV-2 and affected our understanding of SARS-CoV-2 biology, specifically highlighting their relevance for therapeutics development.
- Publisher
- Portland Press
- Keywords
- *SARS-CoV-2/genetics; Humans; *COVID-19/virology; Spike Glycoprotein, Coronavirus/genetics/metabolism/chemistry; Angiotensin-Converting Enzyme 2/metabolism/genetics; Mutation; High-Throughput Nucleotide Sequencing/methods; SARS-CoV-2; deep mutational scanning; multiplexed assays of variant effects; nucleocapsid; spike; viral proteases
- Research Division(s)
- Structural Biology
- PubMed ID
- 40905952
- Publisher's Version
- https://doi.org/10.1042/BST20253033
- Open Access at Publisher's Site
https://doi.org/10.1042/BST20253033- Terms of Use/Rights Notice
- Refer to copyright notice on published article.
Creation Date: 2025-09-23 08:17:32
Last Modified: 2025-11-03 09:25:14