AbstractThe spread of SARS-CoV-2 to animals has the potential to evolve independently. In this study, we distinguished several sentinel animal species and genera for monitoring the re-emergence of COVID-19 or the new outbreak of COVID-19-like disease. We analyzed SARS-CoV-2 genomic data from human and nonhuman mammals in the taxonomic hierarchies of species, genus, family and order of their host.

。在这项研究中，我们区分了几种前哨动物物种和属，用于监测新型冠状病毒肺炎的再次出现或新型冠状病毒肺炎样疾病的新爆发。我们分析了来自人类和非人类哺乳动物的SARS-CoV-2基因组数据，包括物种，属，科和宿主顺序的分类层次。

We find that SARS-CoV-2 carried by domestic dog (Canis lupus familiaris), domestic cat (Felis catus), mink (Neovison vison), and white-tailed deer (Odocoileus virginianus) cluster closely to human-origin viruses and show no differences in the majority of amino acids, but have the most positively selected sites and should be monitored to prevent the re-emergence of COVID-19 caused by novel variants of SARS-CoV-2.

我们发现家犬（犬狼疮）、家猫（猫科动物）、水貂（Neovison vison）和白尾鹿（Odocoileus virginianus）携带的SARS-CoV-2与人类来源的病毒密切相关，大多数氨基酸没有差异，但具有最积极的选择位点，应予以监测，以防止SARS-CoV-2新变异引起的COVID-19再次出现。

Viruses from the genera Panthera (especially lion (Panthera leo)), Manis and Rhinolophus differ significantly from human-origin viruses, and long-term surveillance should be undertaken to prevent the future COVID-19-like outbreaks. Investigation of the variation dynamics of sites 142, 501, 655, 681 and 950 within the S protein may be necessary to predict the novel animal SARS-CoV-2 variants..

。研究S蛋白内位点142、501、655、681和950的变异动力学可能有必要预测新的动物SARS-CoV-2变体。。

IntroductionThe COVID-19 pandemic, which began in 2019, has had a significant impact on the global economy and public health. As of 30 July 2023, more than 768 million confirmed cases and more than 6.9 million deaths had been reported worldwide1. The pathogen, SARS-CoV-2, is a single, positive-stranded, non-segmented RNA virus, and the viral genome can encode at least 29 proteins, of which the spike (S) protein is a critical structural protein involved in recognition and fusion with the host cell receptor angiotensin-converting enzyme 2 (ACE2)2,3.

引言自2019年开始的新型冠状病毒肺炎大流行对全球经济和公共卫生产生了重大影响。截至2023年7月30日，全世界报告的确诊病例超过7.68亿，死亡人数超过690万1。病原体SARS-CoV-2是一种单链正链非节段RNA病毒，病毒基因组可编码至少29种蛋白质，其中棘突蛋白是参与识别的关键结构蛋白。与宿主细胞受体血管紧张素转换酶2（ACE2）2,3融合。

The S protein is composed of two functional regions, S1 and S2. The S1 region contains two crucial structural domains, the N-terminal domain (NTD) and the receptor-binding domain (RBD), which interfere with the immune response of the host cell and recognize and bind to host-associated receptors, respectively, while the S2 region mediates the fusion of the virus with the cell membrane4,5,6.

S蛋白由两个功能区S1和S2组成。S1区域包含两个关键的结构域，即N末端结构域（NTD）和受体结合结构域（RBD），它们分别干扰宿主细胞的免疫应答并识别和结合宿主相关受体，而S2区域介导病毒与细胞膜的融合4,5,6。

It has been demonstrated that the high variability of the RBD and NTD relates to the virus’ immune evasion and host selection7.Coronaviruses have a taxonomically and geographically broad host range and exhibit genetic diversity and frequent gene recombination. Mammals are important potential hosts for cross-species transmission of novel coronaviruses.

已经证明，RBD和NTD的高变异性与病毒的免疫逃避和宿主选择有关7。冠状病毒具有分类学和地理上广泛的宿主范围，并表现出遗传多样性和频繁的基因重组。哺乳动物是新型冠状病毒跨物种传播的重要潜在宿主。

SARS-CoV-2 is widely believed to have originated in bats8,9,10, and previous studies have suggested that pangolins were likely to be its intermediate host due to their high amino acid sequence similarity11,12,13. However, later studies found that their nucleotide sequence was clearly different, so the conclusion that pangolins are intermediate hosts was not conclusive14.

人们普遍认为SARS-CoV-2起源于蝙蝠8,9,10，以前的研究表明，穿山甲可能是其中间宿主，因为它们具有高氨基酸序列相似性11,12,13。然而，后来的研究发现，它们的核苷酸序列明显不同，因此穿山甲是中间宿主的结论并不确定14。

Since the outbreak of the COVID-19 pandemic, numerous infections have been observed in both domestic and wild mammals. Variou.

自新型冠状病毒肺炎爆发以来，在家养和野生哺乳动物中都观察到了许多感染。瓦里欧。

Data availability

数据可用性

Some or all data, models, or code generated or used during the study are available from the corresponding author by request.

研究期间生成或使用的部分或全部数据，模型或代码可根据要求从相应的作者处获得。

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Download referencesAcknowledgementsThis research was funded by the Shanghai New Three-year Action Plan for Public Health (2023-2025, Grant No. GWVI-11.1-03), the National Natural Science Foundation of China (Grants 81872673) and the Three-Year Action Plan of Shanghai Public Health System Construction-Key Discipline Construction (2020-2022, Grant No.

下载参考文献致谢本研究由上海市公共卫生新三年行动计划（2023-2025，批准号GWVI-11.1-03），国家自然科学基金（批准号81872673）和上海市公共卫生系统建设重点学科建设三年行动计划（2020-2022，批准号：。

GWV-10.1-XK03). The funders had no role in study design, data collection, data analysis, data interpretation, or writing of the report.Author informationAuthor notesYanjiao Li, Jingjing Hu, Jingjing Hou and Shuiping Lu contributed equally to this work.Authors and AffiliationsDepartment of Epidemiology, School of Public Health, Fudan University, Shanghai, 200433, ChinaYanjiao Li, Jingjing Hu, Shuiping Lu, Yuxi Wang, Weijie Chen, Yue Pan, Qingwu Jiang, Weibing Wang & Chenglong XiongKey Laboratory of Public Health Safety, Ministry of Education, School of Public Health, Fudan University, Shanghai, 200433, ChinaYanjiao Li, Jingjing Hu, Shuiping Lu, Yuxi Wang, Weijie Chen, Yue Pan, Qingwu Jiang, Weibing Wang & Chenglong XiongDepartment of Pulmonary and Critical Care Medicine, Tongji Hospital, School of Medicine, Tongji University, Shanghai, 200065, ChinaJingjing HouDivision of Emergency Management, Shanghai Municipal Center for Disease Control and Prevention, Shanghai, 200336, ChinaJiasheng XiongDepartment of Biomedical Sciences, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Serdang, 43400, MalaysiaZhong Sun & Karuppiah ThilakavathyDepartment of Integrative Medicine and Neurobiology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, ChinaYi FengAuthorsYanjiao LiView author publicationsYou can also search for this author in.

GWV-10.1-XK03）。资助者在研究设计，数据收集，数据分析，数据解释或撰写报告方面没有任何作用。作者信息作者注：李安娇、胡晶晶、侯晶晶和陆水平对这项工作做出了同样的贡献。作者和所属单位复旦大学公共卫生学院流行病学系，上海，200433，中国李燕娇、胡晶晶、陆水平、王玉溪、陈伟杰、潘岳、蒋清武、王卫兵和成龙熊复旦大学公共卫生学院教育部公共卫生安全重点实验室，上海，200433，李燕娇、胡晶晶、陆水平、王玉溪、陈伟杰、潘岳、蒋清武、王卫兵和熊成龙同济大学医学院同济医院肺与重症监护医学系，上海，200065，中国南京后上海市疾病预防控制中心应急管理处，上海，200336，中国熊家生马来西亚塞尔当普特拉大学医学与健康科学学院生物医学科学系，43400，MalaysiaZhong Sun＆Karuppiah ThilakavathyDepartment of Integrative Medicine and Neurobiology，School of Basic Medical Sciences，复旦大学，上海，200032，ChinaYi Feng作者Yanjiao LiView作者出版物您也可以在中搜索这位作者。

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PubMed Google ScholarContributionsY. L., S. L., J. X. and C. X. wrote the first draft of the paper; Y. L., J. Hou, Y. W. and W. C. performed the literature search; J. Hu, J. X., Z. S. and Y. P. performed the data processing; K. T., Y. F., Q. J., W. W. and C. X. performed the systems review.

PubMed谷歌学术贡献。五十、 ，S.L.，J.X.和C.X.撰写了论文的初稿；Y、 L.，J.Hou，Y.W.和W.C.进行了文献检索；J、 Hu，J.X.，Z.S.和Y.P.进行了数据处理；K、 T.，Y.F.，Q.J.，W.W.和C.X.进行了系统审查。

C.X. and W. W. supervised the study. All authors made substantial revisions and critical review, and all authors have seen and approved the final version.Corresponding authorsCorrespondence to.

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Reprints and permissionsAbout this articleCite this articleLi, Y., Hu, J., Hou, J. et al. Study on sentinel hosts for surveillance of future COVID-19-like outbreaks.

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KeywordsSARS-CoV-2Sentinel hostSpike proteinPhylogenetic treeAmino acid polymorphismPositively selected site

关键词SARS-CoV-2Sentinel hostSpike蛋白植物生成树氨基酸多态性阳性选择位点