A single mutation may contribute to accelerated evolution of SARS-CoV-2 toward Omicron
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 experime...
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Nature Portfolio
2025-07-01
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| Series: | Nature Communications |
| Online Access: | https://doi.org/10.1038/s41467-025-62300-0 |
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| author | 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 Zhenglin Zhu |
| author_facet | 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 Zhenglin Zhu |
| author_sort | Xiaoyuan Lin |
| collection | DOAJ |
| description | 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. |
| format | Article |
| id | doaj-art-88f08bebffd34d38bb68e4bb466434f2 |
| institution | Kabale University |
| issn | 2041-1723 |
| language | English |
| publishDate | 2025-07-01 |
| publisher | Nature Portfolio |
| record_format | Article |
| series | Nature Communications |
| spelling | doaj-art-88f08bebffd34d38bb68e4bb466434f22025-08-20T03:46:17ZengNature PortfolioNature Communications2041-17232025-07-0116111810.1038/s41467-025-62300-0A single mutation may contribute to accelerated evolution of SARS-CoV-2 toward OmicronXiaoyuan Lin0Zhou Sha1Chunlin Zhang2Julia M. Adler3Ricardo Martin Vidal4Christine Langner5Beibei Fu6Yan Xiong7Meng Tan8Chen Jiang9Hao Zeng10Xiaokai Zhang11Qian Li12Jingmin Yan13Xiaoxue Lu14Shiwei Wang15Xuhu Mao16Dusan Kunec17Jakob Trimpert18Haibo Wu19Quanming Zou20Zhenglin Zhu21Department of Clinical Microbiology and Immunology, College of Pharmacy and Medical Laboratory, Army Medical University (Third Military Medical University)School of Life Sciences, Chongqing UniversitySchool of Life Sciences, Chongqing UniversityInstitut für Virologie, Freie Universität BerlinInstitut für Virologie, Freie Universität BerlinInstitut für Virologie, Freie Universität BerlinDepartment of Clinical Microbiology and Immunology, College of Pharmacy and Medical Laboratory, Army Medical University (Third Military Medical University)School of Life Sciences, Chongqing UniversitySchool of Life Sciences, Chongqing UniversitySchool of Life Sciences, Chongqing UniversityNational Engineering Research Center of Immunological, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and Laboratory Medicine, Army Medical University (Third Military Medical University)National Engineering Research Center of Immunological, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and Laboratory Medicine, Army Medical University (Third Military Medical University)Department of Clinical Microbiology and Immunology, College of Pharmacy and Medical Laboratory, Army Medical University (Third Military Medical University)Department of Clinical Microbiology and Immunology, College of Pharmacy and Medical Laboratory, Army Medical University (Third Military Medical University)Department of Clinical Microbiology and Immunology, College of Pharmacy and Medical Laboratory, Army Medical University (Third Military Medical University)Department of Clinical Microbiology and Immunology, College of Pharmacy and Medical Laboratory, Army Medical University (Third Military Medical University)Department of Clinical Microbiology and Immunology, College of Pharmacy and Medical Laboratory, Army Medical University (Third Military Medical University)Institut für Virologie, Freie Universität BerlinInstitut für Virologie, Freie Universität BerlinSchool of Life Sciences, Chongqing UniversityNational Engineering Research Center of Immunological, Department of Microbiology and Biochemical Pharmacy, College of Pharmacy and Laboratory Medicine, Army Medical University (Third Military Medical University)School of Life Sciences, Chongqing UniversityAbstract 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.https://doi.org/10.1038/s41467-025-62300-0 |
| spellingShingle | 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 Zhenglin Zhu A single mutation may contribute to accelerated evolution of SARS-CoV-2 toward Omicron Nature Communications |
| title | A single mutation may contribute to accelerated evolution of SARS-CoV-2 toward Omicron |
| title_full | A single mutation may contribute to accelerated evolution of SARS-CoV-2 toward Omicron |
| title_fullStr | A single mutation may contribute to accelerated evolution of SARS-CoV-2 toward Omicron |
| title_full_unstemmed | A single mutation may contribute to accelerated evolution of SARS-CoV-2 toward Omicron |
| title_short | A single mutation may contribute to accelerated evolution of SARS-CoV-2 toward Omicron |
| title_sort | single mutation may contribute to accelerated evolution of sars cov 2 toward omicron |
| url | https://doi.org/10.1038/s41467-025-62300-0 |
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