A single mutation may contribute to accelerated evolution of SARS-CoV-2 toward Omicron

Xiaoyuan Lin, Zhou Sha, Chunlin Zhang, Julia M. Adler, Ricardo Martin Vidal, Christine Langner, Beibei Fu, Yan Xiong, Meng Tan, Chen Jiang, Hao Zeng, Xiaokai Zhang, Qian Li, Jingmin Yan, Xiaoxue Lu, Shiwei Wang, Xuhu Mao, Dusan Kunec, Jakob Trimpert (), Haibo Wu (), Quanming Zou () and Zhenglin Zhu ()
Additional contact information
Xiaoyuan Lin: Army Medical University (Third Military Medical University)
Zhou Sha: Chongqing University
Chunlin Zhang: Chongqing University
Julia M. Adler: Freie Universität Berlin
Ricardo Martin Vidal: Freie Universität Berlin
Christine Langner: Freie Universität Berlin
Beibei Fu: Army Medical University (Third Military Medical University)
Yan Xiong: Chongqing University
Meng Tan: Chongqing University
Chen Jiang: Chongqing University
Hao Zeng: Army Medical University (Third Military Medical University)
Xiaokai Zhang: Army Medical University (Third Military Medical University)
Qian Li: Army Medical University (Third Military Medical University)
Jingmin Yan: Army Medical University (Third Military Medical University)
Xiaoxue Lu: Army Medical University (Third Military Medical University)
Shiwei Wang: Army Medical University (Third Military Medical University)
Xuhu Mao: Army Medical University (Third Military Medical University)
Dusan Kunec: Freie Universität Berlin
Jakob Trimpert: Freie Universität Berlin
Haibo Wu: Chongqing University
Quanming Zou: Army Medical University (Third Military Medical University)
Zhenglin Zhu: Chongqing University

Nature Communications, 2025, vol. 16, issue 1, 1-18

Abstract: Abstract How SARS-CoV-2 Omicron evolved remains obscure. T492I, an Omicron-specific mutation encountered in SARS-CoV-2 nonstructural protein 4 (NSP4), enhances viral replication and alters nonstructural protein cleavage, inferring potentials to drive evolution. Through evolve-and-resequence experiments of SARS-CoV-2 wild-type (hCoV-19/USA/WA-CDC-02982585-001/2020, A) and Delta strains (B.1.617) with or without T492I, this study demonstrates that the NSP4 mutation T492I confers accelerated phenotypic adaption and a predisposition to the emergence of SARS-CoV-2 Omicron-like variants. The T492I-driven evolution results in accelerated enhancement in viral replication, infectivity, immune evasion capacity, receptor-binding affinity and potential for cross-species transmission. Aside from elevated mutation rates and impact on deaminases, positive epistasis between T492I and adaptive mutations could potentially mechanistically facilitate the shifts in mutation spectra and indirectly determines the Omicron-predisposing evolution. These suggest a potentially important role of the driver mutation T492I in the evolution of SARS-CoV-2 Omicron variants. Our findings highlight the existence and importance of mutation-driven predisposition in viral evolution.

Date: 2025
References: Add references at CitEc
Citations:

Downloads: (external link)
https://www.nature.com/articles/s41467-025-62300-0 Abstract (text/html)

Related works:
This item may be available elsewhere in EconPapers: Search for items with the same title.

Export reference: BibTeX RIS (EndNote, ProCite, RefMan) HTML/Text

Persistent link: https://EconPapers.repec.org/RePEc:nat:natcom:v:16:y:2025:i:1:d:10.1038_s41467-025-62300-0

Ordering information: This journal article can be ordered from
https://www.nature.com/ncomms/

DOI: 10.1038/s41467-025-62300-0

Access Statistics for this article

Nature Communications is currently edited by Nathalie Le Bot, Enda Bergin and Fiona Gillespie

More articles in Nature Communications from Nature
Bibliographic data for series maintained by Sonal Shukla () and Springer Nature Abstracting and Indexing ().