Citation: Wentao Zhu, Yuyuan Huang, Jian Gong, Lingzhi Dong, Xiaojie Yu, Haiyun Chen, Dandan Li, Libo Zhou, Jing Yang, Shan Lu. A novel bat coronavirus with a polybasic furin-like cleavage site .VIROLOGICA SINICA, 2023, 38(3) : 344-350.  http://dx.doi.org/10.1016/j.virs.2023.04.009

A novel bat coronavirus with a polybasic furin-like cleavage site

  • Corresponding author: Jing Yang, yangjing@icdc.cn
    Shan Lu, lushan@icdc.cn
  • Received Date: 07 January 2023
    Accepted Date: 24 April 2023
    Available online: 02 May 2023
  • The current pandemic of COVID-19 caused by a novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), threatens human health around the world. Of particular concern is that bats are recognized as one of the most potential natural hosts of SARS-CoV-2; however, coronavirus ecology in bats is still nascent. Here, we performed a degenerate primer screening and next-generation sequencing analysis of 112 bats, collected from Hainan Province, China. Three coronaviruses, namely bat betacoronavirus (Bat CoV) CD35, Bat CoV CD36 and bat alphacoronavirus CD30 were identified. Bat CoV CD35 genome had 99.5% identity with Bat CoV CD36, both sharing the highest nucleotide identity with Bat Hp-betacoronavirus Zhejiang2013 (71.4%), followed by SARS-CoV-2 (54.0%). Phylogenetic analysis indicated that Bat CoV CD35 formed a distinct clade, and together with Bat Hp-betacoronavirus Zhejiang2013, was basal to the lineage of SARS-CoV-1 and SARS-CoV-2. Notably, Bat CoV CD35 harbored a canonical furin-like S1/S2 cleavage site that resembles the corresponding sites of SARS-CoV-2. The furin cleavage sites between CD35 and CD36 are identical. In addition, the receptor-binding domain of Bat CoV CD35 showed a highly similar structure to that of SARS-CoV-1 and SARS-CoV-2, especially in one binding loop. In conclusion, this study deepens our understanding of the diversity of coronaviruses and provides clues about the natural origin of the furin cleavage site of SARS-CoV-2.

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    1. Almagro Armenteros JJ, Tsirigos KD, Sønderby CK, Petersen TN, Winther O, Brunak S, von Heijne G, Nielsen H (2019) SignalP 5.0 improves signal peptide predictions using deep neural networks. Nat Biotechnol 37:420-423

    2. Buchfink B, Xie C, Huson DH (2015) Fast and sensitive protein alignment using DIAMOND. Nat Methods 12:59-60

    3. Burgin CJ, Colella JP, Kahn PL, Upham NS (2018) How many species of mammals are there? Journal of Mammalogy 99:1-14

    4. Chen L, Liu B, Yang J, Jin Q (2014) DBatVir:the database of bat-associated viruses. Database (Oxford) 2014:bau021

    5. Coutard B, Valle C, de Lamballerie X, Canard B, Seidah NG, Decroly E (2020) The spike glycoprotein of the new coronavirus 2019-nCoV contains a furin-like cleavage site absent in CoV of the same clade. Antiviral Res 176:104742

    6. Duckert P, Brunak S, Blom N (2004) Prediction of proprotein convertase cleavage sites. Protein Eng Des Sel 17:107-112

    7. Frutos R, Serra-Cobo J, Pinault L, Lopez Roig M, Devaux CA (2021) Emergence of Bat-Related Betacoronaviruses:Hazard and Risks. Front Microbiol 12:591535

    8. Ge XY, Wang N, Zhang W, Hu B, Li B, Zhang YZ, Zhou JH, Luo CM, Yang XL, Wu LJ, Wang B, Zhang Y, Li ZX, Shi ZL (2016) Coexistence of multiple coronaviruses in several bat colonies in an abandoned mineshaft. Virol Sin 31:31-40

    9. Grabherr MG, Haas BJ, Yassour M, Levin JZ, Thompson DA, Amit I, Adiconis X, Fan L, Raychowdhury R, Zeng Q, Chen Z, Mauceli E, Hacohen N, Gnirke A, Rhind N, di Palma F, Birren BW, Nusbaum C, Lindblad-Toh K, Friedman N, Regev A (2011) Full-length transcriptome assembly from RNA-Seq data without a reference genome. Nature biotechnology 29:644-652

    10. Guindon S, Dufayard JF, Lefort V, Anisimova M, Hordijk W, Gascuel O (2010) New algorithms and methods to estimate maximum-likelihood phylogenies:assessing the performance of PhyML 3.0. Syst Biol 59:307-321

    11. Hu B, Guo H, Zhou P, Shi ZL (2021) Characteristics of SARS-CoV-2 and COVID-19. Nat Rev Microbiol 19:141-154

    12. Hu D, Zhu C, Ai L, He T, Wang Y, Ye F, Yang L, Ding C, Zhu X, Lv R, Zhu J, Hassan B, Feng Y, Tan W, Wang C (2018) Genomic characterization and infectivity of a novel SARS-like coronavirus in Chinese bats. Emerg Microbes Infect 7:154

    13. Jiang S, Shi ZL (2020) The First Disease X is Caused by a Highly Transmissible Acute Respiratory Syndrome Coronavirus. Virol Sin 35:263-265

    14. Kalyaanamoorthy S, Minh BQ, Wong TKF, von Haeseler A, Jermiin LS (2017) ModelFinder:fast model selection for accurate phylogenetic estimates. Nat Methods 14:587-589

    15. Katoh K, Standley DM (2013) MAFFT multiple sequence alignment software version 7:improvements in performance and usability. Mol Biol Evol 30:772-780

    16. Kido H, Okumura Y, Takahashi E, Pan HY, Wang S, Yao D, Yao M, Chida J, Yano M (2012) Role of host cellular proteases in the pathogenesis of influenza and influenza-induced multiple organ failure. Biochim Biophys Acta 1824:186-194

    17. Lam TT, Jia N, Zhang YW, Shum MH, Jiang JF, Zhu HC, Tong YG, Shi YX, Ni XB, Liao YS, Li WJ, Jiang BG, Wei W, Yuan TT, Zheng K, Cui XM, Li J, Pei GQ, Qiang X, Cheung WY, Li LF, Sun FF, Qin S, Huang JC, Leung GM, Holmes EC, Hu YL, Guan Y, Cao WC (2020) Identifying SARS-CoV-2-related coronaviruses in Malayan pangolins. Nature 583:282-285

    18. Lau SK, Li KS, Tsang AK, Shek CT, Wang M, Choi GK, Guo R, Wong BH, Poon RW, Lam CS, Wang SY, Fan RY, Chan KH, Zheng BJ, Woo PC, Yuen KY (2012) Recent transmission of a novel alphacoronavirus, bat coronavirus HKU10, from Leschenault's rousettes to pomona leaf-nosed bats:first evidence of interspecies transmission of coronavirus between bats of different suborders. J Virol 86:11906-11918

    19. Letko M, Marzi A, Munster V (2020a) Functional assessment of cell entry and receptor usage for SARS-CoV-2 and other lineage B betacoronaviruses. Nat Microbiol 5:562-569

    20. Letko M, Seifert SN, Olival KJ, Plowright RK, Munster VJ (2020b) Bat-borne virus diversity, spillover and emergence. Nat Rev Microbiol 18:461-471

    21. Letunic I, Bork P (2016) Interactive tree of life (iTOL) v3:an online tool for the display and annotation of phylogenetic and other trees. Nucleic Acids Res 44:W242-245

    22. Li B, Si HR, Zhu Y, Yang XL, Anderson DE, Shi ZL, Wang LF, Zhou P (2020) Discovery of Bat Coronaviruses through Surveillance and Probe Capture-Based Next-Generation Sequencing. mSphere 5:e00807-19

    23. Li LL, Wang JL, Ma XH, Sun XM, Li JS, Yang XF, Shi WF, Duan ZJ (2021) A novel SARS-CoV-2 related coronavirus with complex recombination isolated from bats in Yunnan province, China. Emerg Microbes Infect 10:1683-1690

    24. Li MY, Li L, Zhang Y, Wang XS (2020) Expression of the SARS-CoV-2 cell receptor gene ACE2 in a wide variety of human tissues. Infect Dis Poverty 9:45

    25. Quevillon E, Silventoinen V, Pillai S, Harte N, Mulder N, Apweiler R, Lopez R (2005) InterProScan:protein domains identifier. Nucleic Acids Res 33:W116-120

    26. Scialo F, Daniele A, Amato F, Pastore L, Matera MG, Cazzola M, Castaldo G, Bianco A (2020) ACE2:The Major Cell Entry Receptor for SARS-CoV-2. Lung 198:867-877

    27. Singh A, Singh RS, Sarma P, Batra G, Joshi R, Kaur H, Sharma AR, Prakash A, Medhi B (2020) A Comprehensive Review of Animal Models for Coronaviruses:SARS-CoV-2, SARS-CoV, and MERS-CoV. Virol Sin 35:290-304

    28. Sun X, Tse LV, Ferguson AD, Whittaker GR (2010) Modifications to the hemagglutinin cleavage site control the virulence of a neurotropic H1N1 influenza virus. J Virol 84:8683-8690

    29. Temmam S, Vongphayloth K, Baquero E, Munier S, Bonomi M, Regnault B, Douangboubpha B, Karami Y, Chrétien D, Sanamxay D, Xayaphet V, Paphaphanh P, Lacoste V, Somlor S, Lakeomany K, Phommavanh N, Pérot P, Dehan O, Amara F, Donati F, Bigot T, Nilges M, Rey FA, van der Werf S, Brey PT, Eloit M (2022) Bat coronaviruses related to SARS-CoV-2 and infectious for human cells. Nature 604:330-336

    30. Wan Y, Shang J, Graham R, Baric RS, Li F (2020) Receptor Recognition by the Novel Coronavirus from Wuhan:an Analysis Based on Decade-Long Structural Studies of SARS Coronavirus. J Virol 94:e00127-20

    31. Waterhouse A, Bertoni M, Bienert S, Studer G, Tauriello G, Gumienny R, Heer FT, de Beer TAP, Rempfer C, Bordoli L, Lepore R, Schwede T (2018) SWISS-MODEL:homology modelling of protein structures and complexes. Nucleic Acids Res 46:W296-w303

    32. Yang Y, Zheng M, Liu Y, Wang Y, Xu Y, Zhou Y, Sun D, Chen L, Li H (2021) Analysis of Intermediate Hosts and Susceptible Animals of SARS-CoV-2 by Computational Methods. Zoonoses https://doi.org/10.15212/ZOONOSES-2021-0010

    33. Zhou H, Chen X, Hu T, Li J, Song H, Liu Y, Wang P, Liu D, Yang J, Holmes EC, Hughes AC, Bi Y, Shi W (2020) A Novel Bat Coronavirus Closely Related to SARS-CoV-2 Contains Natural Insertions at the S1/S2 Cleavage Site of the Spike Protein. Curr Biol 30:2196-2203.e2193

    34. Zhou P, Yang XL, Wang XG, Hu B, Zhang L, Zhang W, Si HR, Zhu Y, Li B, Huang CL, Chen HD, Chen J, Luo Y, Guo H, Jiang RD, Liu MQ, Chen Y, Shen XR, Wang X, Zheng XS, Zhao K, Chen QJ, Deng F, Liu LL, Yan B, Zhan FX, Wang YY, Xiao GF, Shi ZL (2020) A pneumonia outbreak associated with a new coronavirus of probable bat origin. Nature 579:270-273

    35. Zhu W, Huang Y, Yu X, Chen H, Li D, Zhou L, Huang Q, Liu L, Yang J, Lu S (2022) Discovery and Evolutionary Analysis of a Novel Bat-Borne Paramyxovirus. Viruses 14:288

    36. Zhu W, Song W, Fan G, Yang J, Lu S, Jin D, Luo XL, Pu J, Chen H, Xu J (2021a) Genomic Characterization of a New Coronavirus from Migratory Birds in Jiangxi Province of China. Virol Sin 36:1656-1659

    37. Zhu W, Yang J, Lu S, Jin D, Wu S, Pu J, Luo XL, Liu L, Li Z, Xu J (2021b) Discovery and Evolution of a Divergent Coronavirus in the Plateau Pika From China That Extends the Host Range of Alphacoronaviruses. Front Microbiol 12:755599

    38. Zhu W, Yang J, Lu S, Lan R, Jin D, Luo XL, Pu J, Wu S, Xu J (2021c) Beta- and Novel Delta-Coronaviruses Are Identified from Wild Animals in the Qinghai-Tibetan Plateau, China. Virol Sin 36:402-411

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    A novel bat coronavirus with a polybasic furin-like cleavage site

      Corresponding author: Jing Yang, yangjing@icdc.cn
      Corresponding author: Shan Lu, lushan@icdc.cn
    • a. Department of Infectious Diseases and Clinical Microbiology, Beijing Institute of Respiratory Medicine and Beijing Chao-Yang Hospital, Capital Medical University, Beijing, 100020, China;
    • b. State Key Laboratory of Infectious Disease Prevention and Control, National Institute for Communicable Disease Control and Prevention, Chinese Center for Disease Control and Prevention, Beijing, 102206, China;
    • c. Hainan Provincial Center for Disease Control and Prevention, Haikou, 570203, China;
    • d. Research Units of Discovery of Unknown Bacteria and Function, Chinese Academy of Medical Sciences, Beijing, 100730, China

    Abstract: The current pandemic of COVID-19 caused by a novel coronavirus, severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), threatens human health around the world. Of particular concern is that bats are recognized as one of the most potential natural hosts of SARS-CoV-2; however, coronavirus ecology in bats is still nascent. Here, we performed a degenerate primer screening and next-generation sequencing analysis of 112 bats, collected from Hainan Province, China. Three coronaviruses, namely bat betacoronavirus (Bat CoV) CD35, Bat CoV CD36 and bat alphacoronavirus CD30 were identified. Bat CoV CD35 genome had 99.5% identity with Bat CoV CD36, both sharing the highest nucleotide identity with Bat Hp-betacoronavirus Zhejiang2013 (71.4%), followed by SARS-CoV-2 (54.0%). Phylogenetic analysis indicated that Bat CoV CD35 formed a distinct clade, and together with Bat Hp-betacoronavirus Zhejiang2013, was basal to the lineage of SARS-CoV-1 and SARS-CoV-2. Notably, Bat CoV CD35 harbored a canonical furin-like S1/S2 cleavage site that resembles the corresponding sites of SARS-CoV-2. The furin cleavage sites between CD35 and CD36 are identical. In addition, the receptor-binding domain of Bat CoV CD35 showed a highly similar structure to that of SARS-CoV-1 and SARS-CoV-2, especially in one binding loop. In conclusion, this study deepens our understanding of the diversity of coronaviruses and provides clues about the natural origin of the furin cleavage site of SARS-CoV-2.

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