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The Function and Mechanism of Enterovirus 71 (EV71) 3C Protease

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Abstract

Enterovirus 71 (EV71) is the main pathogen of the hand, foot, and mouth disease. It was firstly isolated from sputum specimens of infants with central nervous system diseases in California in 1969, and has been repeatedly reported in various parts of the world, especially in the Asia-Pacific region. EV71 3C protein is a 183 amino acid cysteine protease that can cleave most structural and non-structural proteins of EV71. Based on the analysis and understanding of EV71 3C protease, it is helpful to study and treat diseases caused by EV71 virus infection. The EV71 3C protease promotes virus replication by cleaving EV71 synthesis or host proteins. Moreover, EV71 3C protease inhibits the innate immune system and causes apoptosis. At present, in order to deal with the damage caused by the EV71, it is urgent to develop antiviral drugs targeting 3C protease. This review will focus on the structure, function, and mechanism of EV71 3C protease.

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References

  1. Yuan J, Shen L, Wu J, Zou X, Gu J, Chen J, Mao L (2018) Enterovirus A71 proteins: structure and function. Front Microbiol 9:286. https://doi.org/10.3389/fmicb.2018.00286

    Article  PubMed  PubMed Central  Google Scholar 

  2. Lin JY, Chen TC, Weng KF, Chang SC, Chen LL, Shih SR (2009) Viral and host proteins involved in picornavirus life cycle. J Biomed Sci 16:103. https://doi.org/10.1186/1423-0127-16-103

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  3. Shih SR, Chiang C, Chen TC, Wu CN, Hsu JT, Lee JC, Hwang MJ, Li ML, Chen GW, Ho MS (2004) Mutations at KFRDI and VGK domains of enterovirus 71 3C protease affect its RNA binding and proteolytic activities. J Biomed Sci 11(2):239–248. https://doi.org/10.1007/bf02256567

    Article  PubMed  CAS  Google Scholar 

  4. Li ML, Hsu TA, Chen TC, Chang SC, Lee JC, Chen CC, Stollar V, Shih SR (2002) The 3C protease activity of enterovirus 71 induces human neural cell apoptosis. Virology 293(2):386–395. https://doi.org/10.1006/viro.2001.1310

    Article  PubMed  CAS  Google Scholar 

  5. Lei X, Liu X, Ma Y, Sun Z, Yang Y, Jin Q, He B, Wang J (2010) The 3C protein of enterovirus 71 inhibits retinoid acid-inducible gene I-mediated interferon regulatory factor 3 activation and type I interferon responses. J Virol 84(16):8051–8061. https://doi.org/10.1128/JVI.02491-09

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  6. Sweeney TR, Roque-Rosell N, Birtley JR, Leatherbarrow RJ, Curry S (2007) Structural and mutagenic analysis of foot-and-mouth disease virus 3C protease reveals the role of the beta-ribbon in proteolysis. J Virol 81(1):115–124. https://doi.org/10.1128/jvi.01587-06

    Article  PubMed  CAS  Google Scholar 

  7. Kuo CJ, Shie JJ, Fang JM, Yen GR, Hsu JT, Liu HG, Tseng SN, Chang SC, Lee CY, Shih SR, Liang PH (2008) Design, synthesis, and evaluation of 3C protease inhibitors as anti-enterovirus 71 agents. Bioorg Med Chem 16(15):7388–7398. https://doi.org/10.1016/j.bmc.2008.06.015

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  8. Sun D, Chen S, Cheng A, Wang M (2016) Roles of the picornaviral 3C proteinase in the viral life cycle and host cells. Viruses 8(3):82. https://doi.org/10.3390/v8030082

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  9. Ank N, West H, Bartholdy C, Eriksson K, Thomsen AR, Paludan SR (2006) Lambda interferon (IFN-lambda), a type III IFN, is induced by viruses and IFNs and displays potent antiviral activity against select virus infections in vivo. J Virol 80(9):4501–4509. https://doi.org/10.1128/jvi.80.9.4501-4509.2006

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  10. Schroder K, Hertzog PJ, Ravasi T, Hume DA (2004) Interferon-gamma: an overview of signals, mechanisms and functions. J Leukoc Biol 75(2):163–189. https://doi.org/10.1189/jlb.0603252

    Article  PubMed  CAS  Google Scholar 

  11. Schoenborn JR, Wilson CB (2007) Regulation of interferon-gamma during innate and adaptive immune responses. Adv Immunol 96:41–101. https://doi.org/10.1016/s0065-2776(07)96002-2

    Article  PubMed  CAS  Google Scholar 

  12. Iwasaki A, Pillai PS (2014) Innate immunity to influenza virus infection. Nat Rev Immunol 14(5):315–328. https://doi.org/10.1038/nri3665

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  13. Tartey S, Takeuchi O (2017) Pathogen recognition and Toll-like receptor targeted therapeutics in innate immune cells. Int Rev Immunol 36(2):57–73. https://doi.org/10.1080/08830185.2016.1261318

    Article  PubMed  CAS  Google Scholar 

  14. Honda K, Taniguchi T (2006) IRFs: master regulators of signalling by Toll-like receptors and cytosolic pattern-recognition receptors. Nat Rev Immunol 6(9):644–658. https://doi.org/10.1038/nri1900

    Article  PubMed  CAS  Google Scholar 

  15. Mishra S, Kumar H (2018) Balancing anti-viral innate immunity and immune homeostasis. Cell Mol Immunol 15(4):408–410. https://doi.org/10.1038/cmi.2017.98

    Article  PubMed  CAS  Google Scholar 

  16. Lei X, Sun Z, Liu X, Jin Q, He B, Wang J (2011) Cleavage of the adaptor protein TRIF by enterovirus 71 3C inhibits antiviral responses mediated by Toll-like receptor 3. J Virol 85(17):8811–8818. https://doi.org/10.1128/jvi.00447-11

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  17. Lei X, Han N, Xiao X, Jin Q, He B, Wang J (2014) Enterovirus 71 3C inhibits cytokine expression through cleavage of the TAK1/TAB1/TAB2/TAB3 complex. J Virol 88(17):9830–9841. https://doi.org/10.1128/jvi.01425-14

    Article  PubMed  PubMed Central  Google Scholar 

  18. Wang C, Ji L, Yuan X, Jin Y, Cardona CJ, Xing Z (2016) Differential regulation of TLR signaling on the induction of antiviral interferons in human intestinal epithelial cells infected with enterovirus 71. PLoS ONE 11(3):e0152177. https://doi.org/10.1371/journal.pone.0152177

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  19. Lei X, Xiao X, Xue Q, Jin Q, He B, Wang J (2013) Cleavage of interferon regulatory factor 7 by enterovirus 71 3C suppresses cellular responses. J Virol 87(3):1690–1698. https://doi.org/10.1128/jvi.01855-12

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  20. Rodriguez KR, Bruns AM, Horvath CM (2014) MDA5 and LGP2: accomplices and antagonists of antiviral signal transduction. J Virol 88(15):8194–8200. https://doi.org/10.1128/jvi.00640-14

    Article  PubMed  PubMed Central  Google Scholar 

  21. Schlee M (2013) Master sensors of pathogenic RNA-RIG-I like receptors. Immunobiology 218(11):1322–1335. https://doi.org/10.1016/j.imbio.2013.06.007

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  22. Chiang JJ, Davis ME, Gack MU (2014) Regulation of RIG-I-like receptor signaling by host and viral proteins. Cytokine Growth Factor Rev 25(5):491–505. https://doi.org/10.1016/j.cytogfr.2014.06.005

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  23. Chen N, Li X, Li P, Pan Z, Ding Y, Zou D, Zheng L, Zhang Y, Li L, Xiao L, Song B, Cui Y, Cao H, Zhang H (2016) Enterovirus 71 inhibits cellular type I interferon signaling by inhibiting host RIG-I ubiquitination. Microb Pathog 100:84–89. https://doi.org/10.1016/j.micpath.2016.09.001

    Article  PubMed  CAS  Google Scholar 

  24. Friedman CS, O'Donnell MA, Legarda-Addison D, Ng A, Cardenas WB, Yount JS, Moran TM, Basler CF, Komuro A, Horvath CM, Xavier R, Ting AT (2008) The tumour suppressor CYLD is a negative regulator of RIG-I-mediated antiviral response. EMBO Rep 9(9):930–936. https://doi.org/10.1038/embor.2008.136

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  25. Xu C, He X, Zheng Z, Zhang Z, Wei C, Guan K, Hou L, Zhang B, Zhu L, Cao Y, Zhang Y, Cao Y, Ma S, Wang P, Zhang P, Xu Q, Ling Y, Yang X, Zhong H (2014) Downregulation of microRNA miR-526a by enterovirus inhibits RIG-I-dependent innate immune response. J Virol 88(19):11356–11368. https://doi.org/10.1128/jvi.01400-14

    Article  PubMed  PubMed Central  Google Scholar 

  26. Wang B, Xi X, Lei X, Zhang X, Cui S, Wang J, Jin Q, Zhao Z (2013) Enterovirus 71 protease 2Apro targets MAVS to inhibit anti-viral type I interferon responses. PLoS Pathog 9(3):e1003231. https://doi.org/10.1371/journal.ppat.1003231

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  27. Feng Q, Langereis MA, Lork M, Nguyen M, Hato SV, Lanke K, Emdad L, Bhoopathi P, Fisher PB, Lloyd RE, van Kuppeveld FJ (2014) Enterovirus 2Apro targets MDA5 and MAVS in infected cells. J Virol 88(6):3369–3378. https://doi.org/10.1128/jvi.02712-13

    Article  PubMed  PubMed Central  Google Scholar 

  28. Kim YK, Shin JS, Nahm MH (2016) NOD-like receptors in infection, immunity, and diseases. Yonsei Med J 57(1):5–14. https://doi.org/10.3349/ymj.2016.57.1.5

    Article  PubMed  CAS  Google Scholar 

  29. Amin J, Boche D, Rakic S (2017) What do we know about the inflammasome in humans? Brain Pathol 27(2):192–204. https://doi.org/10.1111/bpa.12479

    Article  PubMed  PubMed Central  Google Scholar 

  30. Zhou W, Chen C, Chen Z, Liu L, Jiang J, Wu Z, Zhao M, Chen Y (2018) NLRP3: a novel mediator in cardiovascular disease. J Immunol Res 2018:5702103. https://doi.org/10.1155/2018/5702103

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  31. Shi J, Zhao Y, Wang K, Shi X, Wang Y, Huang H, Zhuang Y, Cai T, Wang F, Shao F (2015) Cleavage of GSDMD by inflammatory caspases determines pyroptotic cell death. Nature 526(7575):660–665. https://doi.org/10.1038/nature15514

    Article  PubMed  CAS  Google Scholar 

  32. Gong X, Zhou J, Zhu W, Liu N, Li J, Li L, Jin Y, Duan Z (2012) Excessive proinflammatory cytokine and chemokine responses of human monocyte-derived macrophages to enterovirus 71 infection. BMC Infect Dis 12:224. https://doi.org/10.1186/1471-2334-12-224

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  33. Chen Z, Li R, Xie Z, Huang G, Yuan Q, Zeng J (2014) IL-6, IL-10 and IL-13 are associated with pathogenesis in children with enterovirus 71 infection. Int J Clin Exp Med 7(9):2718–2723

    PubMed  PubMed Central  CAS  Google Scholar 

  34. Kanneganti TD, Body-Malapel M, Amer A, Park JH, Whitfield J, Franchi L, Taraporewala ZF, Miller D, Patton JT, Inohara N, Nunez G (2006) Critical role for Cryopyrin/Nalp3 in activation of caspase-1 in response to viral infection and double-stranded RNA. J Biol Chem 281(48):36560–36568. https://doi.org/10.1074/jbc.M607594200

    Article  PubMed  CAS  Google Scholar 

  35. Wang H, Lei X, Xiao X, Yang C, Lu W, Huang Z, Leng Q, Jin Q, He B, Meng G, Wang J (2015) Reciprocal regulation between enterovirus 71 and the NLRP3 inflammasome. Cell Rep 12(1):42–48. https://doi.org/10.1016/j.celrep.2015.05.047

    Article  PubMed  CAS  Google Scholar 

  36. Platanias LC (2005) Mechanisms of type-I- and type-II-interferon-mediated signalling. Nat Rev Immunol 5(5):375–386. https://doi.org/10.1038/nri1604

    Article  PubMed  CAS  Google Scholar 

  37. Ng CT, Mendoza JL, Garcia KC, Oldstone MB (2016) Alpha and beta type 1 interferon signaling: passage for diverse biologic outcomes. Cell 164(3):349–352. https://doi.org/10.1016/j.cell.2015.12.027

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  38. Ivashkiv LB, Donlin LT (2014) Regulation of type I interferon responses. Nat Rev Immunol 14(1):36–49. https://doi.org/10.1038/nri3581

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  39. Michalska A, Blaszczyk K, Wesoly J, Bluyssen HAR (2018) A positive feedback amplifier circuit that regulates interferon (IFN)-stimulated gene expression and controls type I and type II IFN responses. Front Immunol 9:1135. https://doi.org/10.3389/fimmu.2018.01135

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  40. Garcia MA, Gil J, Ventoso I, Guerra S, Domingo E, Rivas C, Esteban M (2006) Impact of protein kinase PKR in cell biology: from antiviral to antiproliferative action. Microbiol Mol Biol Rev 70(4):1032–1060. https://doi.org/10.1128/mmbr.00027-06

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  41. Silverman RH (1994) Fascination with 2–5A-dependent RNase: a unique enzyme that functions in interferon action. J Interferon Res 14(3):101–104

    Article  CAS  PubMed  Google Scholar 

  42. Goodbourn S, Didcock L, Randall RE (2000) Interferons: cell signalling, immune modulation, antiviral response and virus countermeasures. J Gen Virol 81(Pt 10):2341–2364. https://doi.org/10.1099/0022-1317-81-10-2341

    Article  PubMed  CAS  Google Scholar 

  43. Katze MG, He Y, Gale M Jr (2002) Viruses and interferon: a fight for supremacy. Nat Rev Immunol 2(9):675–687. https://doi.org/10.1038/nri888

    Article  PubMed  CAS  Google Scholar 

  44. Weber F, Kochs G, Haller O (2004) Inverse interference: how viruses fight the interferon system. Viral Immunol 17(4):498–515. https://doi.org/10.1089/vim.2004.17.498

    Article  PubMed  CAS  Google Scholar 

  45. Liu ML, Lee YP, Wang YF, Lei HY, Liu CC, Wang SM, Su IJ, Wang JR, Yeh TM, Chen SH, Yu CK (2005) Type I interferons protect mice against enterovirus 71 infection. J Gen Virol 86(Pt 12):3263–3269. https://doi.org/10.1099/vir.0.81195-0

    Article  PubMed  CAS  Google Scholar 

  46. Lu J, Yi L, Zhao J, Yu J, Chen Y, Lin MC, Kung HF, He ML (2012) Enterovirus 71 disrupts interferon signaling by reducing the level of interferon receptor 1. J Virol 86(7):3767–3776. https://doi.org/10.1128/jvi.06687-11

    Article  PubMed  PubMed Central  Google Scholar 

  47. Liu Y, Zhang Z, Zhao X, Yu R, Zhang X, Wu S, Liu J, Chi X, Song X, Fu L, Yu Y, Hou L, Chen W (2014) Enterovirus 71 inhibits cellular type I interferon signaling by downregulating JAK1 protein expression. Viral Immunol 27(6):267–276. https://doi.org/10.1089/vim.2013.0127

    Article  PubMed  CAS  Google Scholar 

  48. Wang C, Sun M, Yuan X, Ji L, Jin Y, Cardona CJ, Xing Z (2017) Enterovirus 71 suppresses interferon responses by blocking Janus kinase (JAK)/signal transducer and activator of transcription (STAT) signaling through inducing karyopherin-alpha1 degradation. J Biol Chem 292(24):10262–10274. https://doi.org/10.1074/jbc.M116.745729

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  49. Hung HC, Wang HC, Shih SR, Teng IF, Tseng CP, Hsu JT (2011) Synergistic inhibition of enterovirus 71 replication by interferon and rupintrivir. J Infect Dis 203(12):1784–1790. https://doi.org/10.1093/infdis/jir174

    Article  PubMed  CAS  Google Scholar 

  50. Wang SM, Lei HY, Huang KJ, Wu JM, Wang JR, Yu CK, Su IJ, Liu CC (2003) Pathogenesis of enterovirus 71 brainstem encephalitis in pediatric patients: roles of cytokines and cellular immune activation in patients with pulmonary edema. J Infect Dis 188(4):564–570. https://doi.org/10.1086/376998

    Article  PubMed  CAS  Google Scholar 

  51. Yang J, Zhao N, Su NL, Sun JL, Lv TG, Chen ZB (2012) Association of interleukin 10 and interferon gamma gene polymorphisms with enterovirus 71 encephalitis in patients with hand, foot and mouth disease. Scand J Infect Dis 44(6):465–469. https://doi.org/10.3109/00365548.2011.649490

    Article  PubMed  CAS  Google Scholar 

  52. Caine EA, Partidos CD, Santangelo JD, Osorio JE (2013) Adaptation of enterovirus 71 to adult interferon deficient mice. PLoS ONE 8(3):e59501. https://doi.org/10.1371/journal.pone.0059501

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  53. Liao CC, Liou AT, Chang YS, Wu SY, Chang CS, Lee CK, Kung JT, Tu PH, Yu YY, Lin CY, Lin JS, Shih C (2014) Immunodeficient mouse models with different disease profiles by in vivo infection with the same clinical isolate of enterovirus 71. J Virol 88(21):12485–12499. https://doi.org/10.1128/jvi.00692-14

    Article  PubMed  PubMed Central  Google Scholar 

  54. Wang LC, Chen SO, Chang SP, Lee YP, Yu CK, Chen CL, Tseng PC, Hsieh CY, Chen SH, Lin CF (2015) Enterovirus 71 proteins 2A and 3D antagonize the antiviral activity of gamma interferon via signaling attenuation. J Virol 89(14):7028–7037. https://doi.org/10.1128/jvi.00205-15

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  55. Barco A, Feduchi E, Carrasco L (2000) Poliovirus protease 3C(pro) kills cells by apoptosis. Virology 266(2):352–360. https://doi.org/10.1006/viro.1999.0043

    Article  PubMed  CAS  Google Scholar 

  56. Weng KF, Li ML, Hung CT, Shih SR (2009) Enterovirus 71 3C protease cleaves a novel target CstF-64 and inhibits cellular polyadenylation. PLoS Pathog 5(9):e1000593. https://doi.org/10.1371/journal.ppat.1000593

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  57. Lei X, Zhang Z, Xiao X, Qi J, He B, Wang J (2017) Enterovirus 71 inhibits pyroptosis through cleavage of gasdermin D. J Virol. https://doi.org/10.1128/jvi.01069-17

    Article  PubMed  PubMed Central  Google Scholar 

  58. Li J, Yao Y, Chen Y, Xu X, Lin Y, Yang Z, Qiao W, Tan J (2017) Enterovirus 71 3C promotes apoptosis through cleavage of PinX1, a telomere binding protein. J Virol. https://doi.org/10.1128/jvi.02016-16

    Article  PubMed  PubMed Central  Google Scholar 

  59. Chen SC, Chang LY, Wang YW, Chen YC, Weng KF, Shih SR, Shih HM (2011) Sumoylation-promoted enterovirus 71 3C degradation correlates with a reduction in viral replication and cell apoptosis. J Biol Chem 286(36):31373–31384. https://doi.org/10.1074/jbc.M111.254896

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  60. Wang T, Wang B, Huang H, Zhang C, Zhu Y, Pei B, Cheng C, Sun L, Wang J, Jin Q, Zhao Z (2017) Enterovirus 71 protease 2Apro and 3Cpro differentially inhibit the cellular endoplasmic reticulum-associated degradation (ERAD) pathway via distinct mechanisms, and enterovirus 71 hijacks ERAD component p97 to promote its replication. PLoS Pathog 13(10):e1006674. https://doi.org/10.1371/journal.ppat.1006674

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  61. Hayden FG, Turner RB, Gwaltney JM, Chi-Burris K, Gersten M, Hsyu P, Patick AK, Smith GJ 3rd, Zalman LS (2003) Phase II, randomized, double-blind, placebo-controlled studies of ruprintrivir nasal spray 2-percent suspension for prevention and treatment of experimentally induced rhinovirus colds in healthy volunteers. Antimicrob Agents Chemother 47(12):3907–3916

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  62. Zhai Y, Ma Y, Ma F, Nie Q, Ren X, Wang Y, Shang L, Yin Z (2016) Structure-activity relationship study of peptidomimetic aldehydes as enterovirus 71 3C protease inhibitors. Eur J Med Chem 124:559–573. https://doi.org/10.1016/j.ejmech.2016.08.064

    Article  PubMed  CAS  Google Scholar 

  63. Wang Y, Yang B, Zhai Y, Yin Z, Sun Y, Rao Z (2015) Peptidyl aldehyde NK-1.8k suppresses enterovirus 71 and enterovirus 68 infection by targeting protease 3C. Antimicrob Agents Chemother 59(5):2636–2646. https://doi.org/10.1128/aac.00049-15

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  64. Zeng D, Ma Y, Zhang R, Nie Q, Cui Z, Wang Y, Shang L, Yin Z (2016) Synthesis and structure-activity relationship of alpha-keto amides as enterovirus 71 3C protease inhibitors. Bioorg Med Chem Lett 26(7):1762–1766. https://doi.org/10.1016/j.bmcl.2016.02.039

    Article  PubMed  CAS  Google Scholar 

  65. Zhang L, Huang G, Cai Q, Zhao C, Tang L, Ren H, Li P, Li N, Huang J, Chen X, Guan Y, You H, Chen S, Li J, Lin T (2016) Optimize the interactions at S4 with efficient inhibitors targeting 3C proteinase from enterovirus 71. J Mol Recogn 29(11):520–527. https://doi.org/10.1002/jmr.2551

    Article  CAS  Google Scholar 

  66. Lin YJ, Chang YC, Hsiao NW, Hsieh JL, Wang CY, Kung SH, Tsai FJ, Lan YC, Lin CW (2012) Fisetin and rutin as 3C protease inhibitors of enterovirus A71. J Virol Methods 182(1–2):93–98. https://doi.org/10.1016/j.jviromet.2012.03.020

    Article  PubMed  CAS  Google Scholar 

  67. Wang J, Zhang T, Du J, Cui S, Yang F, Jin Q (2014) Anti-enterovirus 71 effects of chrysin and its phosphate ester. PLoS ONE 9(3):e89668. https://doi.org/10.1371/journal.pone.0089668

    Article  PubMed  PubMed Central  CAS  Google Scholar 

  68. Zhai Y, Zhao X, Cui Z, Wang M, Wang Y, Li L, Sun Q, Yang X, Zeng D, Liu Y, Sun Y, Lou Z, Shang L, Yin Z (2015) Cyanohydrin as an anchoring group for potent and selective inhibitors of enterovirus 71 3C protease. J Med Chem 58(23):9414–9420. https://doi.org/10.1021/acs.jmedchem.5b01013

    Article  PubMed  CAS  Google Scholar 

  69. Shang L, Wang Y, Qing J, Shu B, Cao L, Lou Z, Gong P, Sun Y, Yin Z (2014) An adenosine nucleoside analogue NITD008 inhibits EV71 proliferation. Antiviral Res 112:47–58. https://doi.org/10.1016/j.antiviral.2014.10.009

    Article  PubMed  CAS  Google Scholar 

  70. Ma GH, Ye Y, Zhang D, Xu X, Si P, Peng JL, Xiao YL, Cao RY, Yin YL, Chen J, Zhao LX, Zhou Y, Zhong W, Liu H, Luo XM, Chen LL, Shen X (2016) Identification and biochemical characterization of DC07090 as a novel potent small molecule inhibitor against human enterovirus 71 3C protease by structure-based virtual screening. Eur J Med Chem 124:981–991. https://doi.org/10.1016/j.ejmech.2016.10.019

    Article  PubMed  CAS  Google Scholar 

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Acknowledgements

This work was supported by National Natural Science Foundation of China Grants 81660332, Natural Science Foundation of Jiangxi province Grants 20151BAB205057 and Health and family planning project of Jiangxi province Grants 20155634.

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  1. Weihui Wen and Zixuan Qi are joint first authors.

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  1. Department of Microbiology, School of Medicine, Nanchang University, Nanchang, Jiangxi, People’s Republic of China

    Weihui Wen & Jing Wang

  2. School of Medicine, Forth Clinical College, Nanchang University, Nanchang, Jiangxi, People’s Republic of China

    Zixuan Qi

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Weihui Wen and Zixuan Qi drafted the manuscript together and Jing Wang was responsible for conception and design.

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Wen, W., Qi, Z. & Wang, J. The Function and Mechanism of Enterovirus 71 (EV71) 3C Protease. Curr Microbiol 77, 1968–1975 (2020). https://doi.org/10.1007/s00284-020-02082-4

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