Multi-omics analysis of attenuated variant reveals potential evaluation marker of host damaging for SARS-CoV-2 variants  

作　　者：Guangshan Xie Lin Zhu Siwen Liu Cun Li Xin Diao Yanhao Zhang Xiuli Su Yuanyuan Song Guodong Cao Li Zhong Pui Wang Xiaojuan Liu Bobo Wing-Yee Mok Shusheng Zhang Dong-Yan Jin Jie Zhou Honglin Chen Zongwei Cai 

机构地区：[1]State Key Laboratory of Environmental and Biological Analysis,Hong Kong Baptist University,Hong Kong SAR,China [2]State Key Laboratory for Emerging Infectious Diseases,and Department of Microbiology,Li Ka Shing Faculty of Medicine,The University of Hong Kong,Hong Kong SAR,China [3]College of Chemistry,Zhengzhou University,Zhengzhou 450001,China [4]School of Biomedical Sciences,The University of Hong Kong,Hong Kong SAR,China [5]HKBU Shenzhen Institute of Research and Continuing Education,Shenzhen 518000,China

出　　处：《Science China(Life Sciences)》2024年第1期83-95,共13页中国科学（生命科学英文版）

基　　金：This work was supported by the National Natural Science Foundation of China(21705137);the Theme-based Research Scheme(TRS,T11-709/21-N);the Collaborative Research Fund(CRF,C7042-21G)of the Research Grants Council of the HKSAR government;the Tier 1 Research Start-up Grants from Research Committee of Hong Kong Baptist University(162874).

摘　　要：SARS-CoV-2 continues to threaten human society by generating novel variants via mutation and recombination.The high number of mutations that appeared in emerging variants not only enhanced their immune-escaping ability but also made it difficult to predict the pathogenicity and virulence based on viral nucleotide sequences.Molecular markers for evaluating the pathogenicity of new variants are therefore needed.By comparing host responses to wild-type and variants with attenuated pathogenicity at proteome and metabolome levels,six key molecules on the polyamine biosynthesis pathway including putrescine,SAM,dc-SAM,ODC1,SAMS,and SAMDC were found to be differentially upregulated and associated with pathogenicity of variants.To validate our discovery,human airway organoids were subsequently used which recapitulates SARS-CoV-2 replication in the airway epithelial cells of COVID-19 patients.Using ODC1 as a proof-ofconcept,differential activation of polyamine biosynthesis was found to be modulated by the renin-angiotensin system(RAS)and positively associated with ACE2 activity.Further experiments demonstrated that ODC1 expression could be differentially activated upon a panel of SARS-CoV-2 variants of concern(VOCs)and was found to be correlated with each VOCs’pathogenic properties.Particularly,the presented study revealed the discriminative ability of key molecules on polyamine biosynthesis as a predictive marker for virulence evaluation and assessment of SARS-CoV-2 variants in cell or organoid models.Our work,therefore,presented a practical strategy that could be potentially applied as an evaluation tool for the pathogenicity of current and emerging SARS-CoV-2 variants.

关 键 词：SARS-CoV-2 multi-omics attenuated variant predictive pathogenic marker polyamine biosynthesis 

分 类 号：R373[医药卫生—病原生物学]