Skip to main content
Springer Nature - PMC COVID-19 Collection logoLink to Springer Nature - PMC COVID-19 Collection
. 2009;8:101–130. doi: 10.1007/978-90-481-2348-3_6

Picornaviruses

David Neubauer 3, Jutta Steinberger 3, Tim Skern 3
Editors: Uwe Lendeckel1, Nigel M Hooper2
PMCID: PMC7122559

Abstract

The picornavirus family contains several major human and animal pathogens. Vaccines against some of these pathogens are available. However, the availability of potent antiviral compounds would be an appreciable advantage in fighting these pathogens. Inside their non-enveloped capsid, picornaviruses possess a positive sense RNA genome with a single open reading frame. Upon release into the cytoplasm, the genome is translated into a single polyprotein that is processed by virally encoded proteinases. These proteinases represent excellent targets for the development of anti-virals for two reasons. First, efficient polyprotein processing is essential for successful viral replication. Second, the picornaviral proteinases show notable differences to cellular proteinases. To aid in the development of anti-virals, detailed knowledge of the mechanisms, substrate specificities and structures of these proteinases is needed. This chapter reviews recent progress, discusses selected substances with antiviral activity against picornavirus proteinases and outlines several new avenues for the design of novel anti-virals.

Keywords: Poliovirus, human rhinovirus, aphthovirus, proteolytic processing, translational control

References

  1. Allaire M., Chernaia M.M, Malcolm B.A., James M.N.G. Picornaviral 3C cysteine proteinases have a fold similar to chymotrypsin-like serine proteinases. Nature. 1994;369:72–76. doi: 10.1038/369072a0. [DOI] [PubMed] [Google Scholar]
  2. Almstead L.L., Sarnow P. Inhibition of U snRNP assembly by a virus-encoded protei-nase. Genes Dev. 2007;21:1086–1097. doi: 10.1101/gad.1535607. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Andino R., Rieckhof G.E., Baltimore D. A functional ribonucleoprotein complex forms around the 5′ end of poliovirus RNA. Cell. 1990;63:369–380. doi: 10.1016/0092-8674(90)90170-j. [DOI] [PubMed] [Google Scholar]
  4. Andrianarivelo M.R., Rabarijaona L., Boisier P., Chezzi C., Zeller H.G. Wild polio-virus circulation among healthy children immunized with oral polio vaccine in antananarivo. Madagascar Trop Med Int Health. 1999;4:50–57. doi: 10.1046/j.1365-3156.1999.00350.x. [DOI] [PubMed] [Google Scholar]
  5. Anon Progress toward interruption of wild poliovirus transmission — Worldwide, January 2007–May 2008. Morbidity and Mortality Weekly Report of the CDC. 2008;57:489–494. [PubMed] [Google Scholar]
  6. Argos P., Kamer G., Nickelin M.J.H., Wimmer E. Similarity in gene organisation and homology between proteins of animal picornaviruses and a plant comovirus suggest a common ancestry of these virus families. Nucl Acids Res. 1984;12:7251–7267. doi: 10.1093/nar/12.18.7251. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Armer H., Moffat K., Wileman T., Belsham G.J., Jackson T., Duprex W.P., Ryan M., Monaghan P. Foot-and-mouth disease virus, but not bovine enterovirus, targets the host cell cytoskeleton via the nonstructural protein 3Cpro. J Virol. 2008;82:10556–10566. doi: 10.1128/JVI.00907-08. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Arruda E., Pitkaranta A., Witek T.A., Jr, Doyle C.A., Hayden F.G. Frequency and natural history of rhinovirus infections in adults during autumn. J Clin Microbiol. 1997;35:2864–2868. doi: 10.1128/jcm.35.11.2864-2868.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Atkins J.F., Wills N.M., Loughran G., Wu C.Y., Parsawar K., Ryan M.D., Wang C.H., Nelson C.C. A case for “StopGo”: reprogramming translation to augment codon meaning of GGN by promoting unconventional termination (Stop) after addition of glycine and then allowing continued translation (Go) RNA. 2007;13:803–810. doi: 10.1261/rna.487907. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Aylward R.B., Sutter R.W., Heymann D.L. Policy. OPV cessation — the final step to a “polio-free” world. Science. 2005;310:625–626. doi: 10.1126/science.1115547. [DOI] [PubMed] [Google Scholar]
  11. Baboonian C., Davies M.J., Booth C., McKenna W.J. Coxsackie B viruses and human heart disease. Curr Top Microbiol Immunol. 1997;223:31–52. doi: 10.1007/978-3-642-60687-8_3. [DOI] [PubMed] [Google Scholar]
  12. Badorff C., Knowlton K.U. Dystrophin disruption in enterovirus-induced myocarditis and dilated cardiomyopathy: from bench to bedside. Med Microbiol Immunol. 2004;193:121–126. doi: 10.1007/s00430-003-0189-7. [DOI] [PubMed] [Google Scholar]
  13. Badorff C., Lee G.H., Lamphear B.J., Martone M.E., Campbell K.P., Rhoads R.E., Knowlton K.U. Enteroviral protease 2A cleaves dystrophin: evidence of cytoskeletal disruption in an acquired cardiomyopathy. Nature Med. 1999;5:320–326. doi: 10.1038/6543. [DOI] [PubMed] [Google Scholar]
  14. Badorff C., Berkely N., Mehrotra S., Talhouk J.W., Rhoads R.E., Knowlton K.U. Enteroviral protease 2A directly cleaves dystrophin and is inhibited by a dystrophin-based substrate analogue. J Biol Chem. 2000;275:11191–11197. doi: 10.1074/jbc.275.15.11191. [DOI] [PubMed] [Google Scholar]
  15. Baxter N.J., Roetzer A., Liebig H.D., Sedelnikova S.E., Hounslow A.M., Skern T., Waltho J.P. Structure and dynamics of coxsackievirus B4 2A proteinase, an enzyme involved in the etiology of heart disease. J Virol. 2006;80:1451–1462. doi: 10.1128/JVI.80.3.1451-1462.2006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Bazan J.F., Fletterick R.J. Viral cysteine proteases are homologous to the trypsin-like family of serine proteases: structural and functional implications. Proc Natl Acad Sci USA. 1988;85:7872–7876. doi: 10.1073/pnas.85.21.7872. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Belsham G.J., McInerney G.M., Ross-Smith N. Foot-and-mouth disease virus 3C protease induces cleavage of translation initiation factors eIF4A and eIF4G within infected cells. J Virol. 2000;74:272–280. doi: 10.1128/jvi.74.1.272-280.2000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Bergmann E.M., Mosimann S.C., Chernaia M.M., Malcolm B.A., James M.N.G. The refined crystal structure of the 3C gene product from hepatitis A virus: specific proteinase activity and RNA recognition. J Virol. 1997;71:2436–2448. doi: 10.1128/jvi.71.3.2436-2448.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Binford S.L., Maldonado F., Brothers M.A., Weady P.T., Zalman L.S., Meador J.W., 3rd, Matthews D.A., Patick A.K. Conservation of amino acids in human rhinovirus 3C protease correlates with broad-spectrum antiviral activity of rupintrivir, a novel human rhino-virus 3C protease inhibitor. Antimicrob Agents Chemother. 2005;49:619–626. doi: 10.1128/AAC.49.2.619-626.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Birtley J.R., Knox S.R., Jaulent A.M., Brick P., Leatherbarrow R.J., Curry S. Crystal structure of foot-and-mouth disease virus 3C protease. New insights into catalytic mechanism and cleavage specificity. J Biol Chem. 2005;280:11520–11527. doi: 10.1074/jbc.M413254200. [DOI] [PubMed] [Google Scholar]
  21. Bjorndahl T.C., Andrew L.C., Semenchenko V., Wishart D.S. NMR solution structures of the apo and peptide-inhibited human rhinovirus 3C protease (Serotype 14): structural and dynamic comparison. Biochemistry. 2007;46:12945–12958. doi: 10.1021/bi7010866. [DOI] [PubMed] [Google Scholar]
  22. Brundage S.C., Fitzpatrick A.N. Hepatitis A. Am Fam Physician. 2006;73:2162–2168. [PubMed] [Google Scholar]
  23. Cencic R., Mayer C., Juliano M.A., Juliano L., Konrat R., Kontaxis G., Skern T. Investigating the substrate specificity and oligomerisation of the leader protease of foot and mouth disease virus using NMR. J Mol Biol. 2007;373:1071–1087. doi: 10.1016/j.jmb.2007.08.061. [DOI] [PubMed] [Google Scholar]
  24. Clamp M., Cuff J., Searle S.M., Barton G.J. The Jalview Java alignment editor. Bioinformatics. 2004;20:426–427. doi: 10.1093/bioinformatics/btg430. [DOI] [PubMed] [Google Scholar]
  25. Collett M.S., Neyts J., Modlin J.F. A case for developing antiviral drugs against polio. Antiviral Res. 2008;79:179–187. doi: 10.1016/j.antiviral.2008.04.002. [DOI] [PubMed] [Google Scholar]
  26. Crowder S., Kirkegaard K. Trans-dominant inhibition of RNA viral replication can slow growth of drug-resistant viruses. Nat Genet. 2005;37:701–709. doi: 10.1038/ng1583. [DOI] [PubMed] [Google Scholar]
  27. Curry S., Roque-Rosell N., Sweeney T.R., Zunszain P.A., Leatherbarrow R.J. Structural analysis of foot-and-mouth disease virus 3C protease: a viable target for antiviral drugs. Biochem Soc Trans. 2007;35:594–598. doi: 10.1042/BST0350594. [DOI] [PubMed] [Google Scholar]
  28. De Lano W.L. The PyMOL Molecular Graphics System. San Carlos, CA.: DeLano Scientific; 2002. [Google Scholar]
  29. de Los Santos T., de Avila Botton S., Weiblen R., Grubman M.J. The leader protein-ase of foot-and-mouth disease virus inhibits the induction of beta interferon mRNA and blocks the host innate immune response. J Virol. 2006;80:1906–1914. doi: 10.1128/JVI.80.4.1906-1914.2006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. De Palma A.M., Vliegen I., De Clercq E., Neyts J. Selective inhibitors of picornavi-rus replication. Med Res Rev. 2008;28:823–884. doi: 10.1002/med.20125. [DOI] [PubMed] [Google Scholar]
  31. Deszcz L., Seipelt J., Vassilieva E., Roetzer A., Kuechler E. Antiviral activity of caspase inhibitors: effect on picornaviral 2A proteinase. FEBS Lett. 2004;560:51–55. doi: 10.1016/S0014-5793(04)00069-9. [DOI] [PubMed] [Google Scholar]
  32. Deszcz L., Cencic R., Sousa C., Kuechler E., Skern T. An anti-viral peptide inhibitor active against picornaviral 2A proteinases but not cellular caspases. J Virol. 2006;80:9619–9627. doi: 10.1128/JVI.00612-06. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Devaney M.A., Vakharia V.N., Lloyd R.E., Ehrenfeld E., Grubman M.J. Leader protein of foot-and-mouth disease virus is required for cleavage of the p220 component of the cap-binding protein complex. J Virol. 1988;62:4407–4409. doi: 10.1128/jvi.62.11.4407-4409.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  34. Dragovich P.S., Webber S.E., Babine R.E., Fuhrman S.A., Patick A.K., Matthews D.A., Lee C.A., Reich S.H., Prins T.J., Marakovits J.T., Littlefield E.S., Zhou R., Tikhe J., Ford C.E., Wallace M.B., Meador J.W.R., Ferre R.A., Brown E.L., Binford S.L., Harr J.E., De Lisle D.M., Worland S.T. Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. 1. Michael acceptor structure-activity studies. J Med Chem. 1998;41:2806–2818. doi: 10.1021/jm980068d. [DOI] [PubMed] [Google Scholar]
  35. Dragovich P.S., Webber S.E., Babine R.E., Fuhrman S.A., Patick A.K., Matthews D.A., Reich S.H., Marakovits J.T., Prins T.J., Zhou R., Tikhe J., Littlefield E.S., Bleckman T.M., Wallace M.B., Little T.L., Ford C.E., Meador J.W.R., Ferre R.A., Brown E.L., Binford S.L., DeLisle D.M., Worland S.T. Structure-based design, synthesis, and biological evaluation of irreversible human rhinovirus 3C protease inhibitors. 2. Peptide structure-activity studies. J Med Chem. 1998;41:2819–2834. doi: 10.1021/jm9800696. [DOI] [PubMed] [Google Scholar]
  36. Duechler M, Skern T., Sommergruber W., Neubauer C., Gruendler P., Fogy I., Blaas D., Kuechler E. Evolutionary relationships within the human rhinovirus genus: comparison of serotypes 89, 2, and 14. Proc Natl Acad Sci USA. 1987;84:2605–2609. doi: 10.1073/pnas.84.9.2605. [DOI] [PMC free article] [PubMed] [Google Scholar]
  37. Falk M.M., Grigera P.R., Bergmann I.E., Zibert A., Multhaup G., Beck E. Foot-and-mouth disease virus protease-3C induces specific proteolytic cleavage of host cell histone-H3. J Virol. 1990;64:748–756. doi: 10.1128/jvi.64.2.748-756.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  38. Ferrer-Orta C., Arias A., Perez-Luque R., Escarmis C., Domingo E., Verdaguer N. Sequential structures provide insights into the fidelity of RNA replication. Proc Natl Acad Sci USA. 2007;104:9463–9468. doi: 10.1073/pnas.0700518104. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. Foeger N., Glaser W., Skern T. Recognition of eukaryotic initiation factor 4G isoforms by picornaviral proteinases. J Biol Chem. 2002;277:44300–44309. doi: 10.1074/jbc.M208006200. [DOI] [PubMed] [Google Scholar]
  40. Foeger N., Schmid E.M., Skern T. Human rhinovirus 2 2Apro recognition of eukaryo-tic initiation factor 4GI. Involvement of an exosite. J Biol Chem. 2003;278:33200–32007. doi: 10.1074/jbc.M304007200. [DOI] [PubMed] [Google Scholar]
  41. Foeger N., Kuehnel E., Cencic R., Skern T. The binding of foot-and-mouth disease virus leader proteinase to eIF4GI involves conserved ionic interactions. FEBS J. 2005;272:2602–2611. doi: 10.1111/j.1742-4658.2005.04689.x. [DOI] [PubMed] [Google Scholar]
  42. Glaser W., Cencic R., Skern T. Foot-and-mouth disease Leader proteinase: involvement of C-terminal residues in self-processing and cleavage of eIF4GI. J Biol Chem. 2001;276:35473–35481. doi: 10.1074/jbc.M104192200. [DOI] [PubMed] [Google Scholar]
  43. Glaser W., Triendl A., Skern T. The processing of eIF4GI by human rhinovirus 2 2Apro: relationship to self-cleavage and role of zinc. J Virol. 2003;77:5021–5025. doi: 10.1128/JVI.77.8.5021-5025.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  44. Gorbalenya A., Svitkin Y. Protease of encephalomyocarditis virus: purification and role of the SH groups in processing of the structural proteins precursor. Biochemistry (USSR) 1983;48:385–395. [Google Scholar]
  45. Gorbalenya A.E., Donchenko A.P., Blinov V.M., Koonin E.V. Cysteine proteases of positive strand RNA viruses and chymotrypsin-like serine proteases. A distinct protein super-family with a common structural fold. FEBS Lett. 1989;243:103–114. doi: 10.1016/0014-5793(89)80109-7. [DOI] [PubMed] [Google Scholar]
  46. Gorbalenya A.E., Koonin E.V., Lai M.M. Putative papain-related thiol proteases of positive-strand RNA viruses. Identification of rubi- and aphthovirus proteases and delineation of a novel conserved domain associated with proteases of rubi-, alpha- and coronaviruses. FEBS Lett. 1991;288:201–205. doi: 10.1016/0014-5793(91)81034-6. [DOI] [PMC free article] [PubMed] [Google Scholar]
  47. Gouvea I.E., Judice W.A., Cezari M.H., Juliano M.A., Juhasz T., Szeltner Z., Polgar L., Juliano L. Kosmotropic salt activation and substrate specificity of poliovirus protease 3C. Biochemistry. 2006;45:12083–12089. doi: 10.1021/bi060793n. [DOI] [PubMed] [Google Scholar]
  48. Gradi A., Svitkin Y.V., Imataka H., Sonenberg N. Proteolysis of human eukaryotic translation initiation factor eIF4GII, but not eIF4GI, coincides with the shutoff of host protein synthesis after poliovirus infection. Proc Natl Acad Sci USA. 1998;95:11089–11094. doi: 10.1073/pnas.95.19.11089. [DOI] [PMC free article] [PubMed] [Google Scholar]
  49. Gradi A., Imataka H., Svitkin Y.V., Rom E., Raught B., Morino S., Sonenberg N. A novel functional human eukaryotic translation initiation factor 4G. Mol Cell Biol. 1998;18:334–342. doi: 10.1128/mcb.18.1.334. [DOI] [PMC free article] [PubMed] [Google Scholar]
  50. Gradi A., Svitkin Y.V., Sommergruber W., Imataka H., Morino S., Skern T., Sonenberg N. Human rhinovirus 2A proteinase cleavage sites in eukaryotic initiation factors (eIF) 4GI and eIF4GII are different. J Virol. 2003;77:5026–5029. doi: 10.1128/JVI.77.8.5026-5029.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  51. Gradi A., Foeger N., Strong R., Svitkin Y.V., Sonenberg N., Skern T., Belsham G. Cleavage of eukaryotic translation initiation factor 4GII within foot-and-mouth disease virus-infected cells: identification of the L-protease cleavage site in vitro. J Virol. 2004;78:3271–3278. doi: 10.1128/JVI.78.7.3271-3278.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  52. Graham K.L., Gustin K.E., Rivera C., Kuyumcu-Martinez N.M., Choe S.S., Lloyd R.E., Sarnow P., Utz P.J. Proteolytic cleavage of the catalytic subunit of DNA-dependent protein kinase during poliovirus infection. J Virol. 2004;78:6313–6321. doi: 10.1128/JVI.78.12.6313-6321.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  53. Grubman M.J., Baxt B. Foot-and-mouth disease. Clin Microbiol Rev. 2004;17:465–493. doi: 10.1128/CMR.17.2.465-493.2004. [DOI] [PMC free article] [PubMed] [Google Scholar]
  54. A. Guarné, Tormo J., Kirchweger K., Pfistermueller D., Fita I., Skern T. Structure of the foot-and-mouth disease virus leader protease: a papain-like fold adapted for self-processing and eIF4G recognition. EMBO J. 1998;17:7469–7479. doi: 10.1093/emboj/17.24.7469. [DOI] [PMC free article] [PubMed] [Google Scholar]
  55. Gustin K.E., Sarnow P. Effects of poliovirus infection on nucleo-cytoplasmic trafficking and nuclear pore complex composition. EMBO J. 2001;20:240–249. doi: 10.1093/emboj/20.1.240. [DOI] [PMC free article] [PubMed] [Google Scholar]
  56. Hansen J.L., Long A.M., Schultz S.C. Structure of the RNA-dependent RNA polymerase of poliovirus. Structure. 1997;5:1109–1122. doi: 10.1016/s0969-2126(97)00261-x. [DOI] [PubMed] [Google Scholar]
  57. Harki D.A., Graci J.D., Galarraga J.E., Chain W.J., Cameron C.E., Peterson B.R. Synthesis and antiviral activity of 5-substituted cytidine analogues: identification of a potent inhibitor of viral RNA-dependent RNA polymerases. J Med Chem. 2006;49:6166–6169. doi: 10.1021/JM060872x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  58. Hayden F.G., Turner R.B., Gwaltney G.M., Chi-Burris K., Gersten M., Hsyu P., Patick A.K., Smith G.J., 3rd, Zalman L.S. Phase II, randomized, double-blind, placebo-controlled studies of rupintrivir nasal spray 2-percent suspension for prevention and treatment of experimentally induced rhinovirus colds in healthy volunteers. Antimicrob Agents Chemother. 2003;47:3907–3916. doi: 10.1128/AAC.47.12.3907-3916.2003. [DOI] [PMC free article] [PubMed] [Google Scholar]
  59. Huitema C., Zhang J., Yin J., James M.N., Vederas J.C., Eltis L.D. Heteroaromatic ester inhibitors of hepatitis A virus 3C proteinase: evaluation of mode of action. Bioorg Med Chem. 2008;16:5761–5777. doi: 10.1016/j.bmc.2008.03.059. [DOI] [PMC free article] [PubMed] [Google Scholar]
  60. Joachims M., Harris K.S., Etchison D. Poliovirus protease 3C mediates cleavage of microtubule-associated protein 4. Virology. 1995;211:451–461. doi: 10.1006/viro.1995.1427. [DOI] [PubMed] [Google Scholar]
  61. Joachims M., Van Breugel P.C., Lloyd R.E. Cleavage of poly(A)-binding protein by enterovirus proteases concurrent with inhibition of translation in vitro. J Virol. 1999;73:718–727. doi: 10.1128/jvi.73.1.718-727.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  62. Johnston S.L., Bardin P.G., Pattemore P.K. Review - viruses as precipitants of asthma symptoms.3. Rhinoviruses - molecular biology and prospects for future intervention. Clin Exp Allergy. 1993;23:237–246. doi: 10.1111/j.1365-2222.1993.tb00316.x. [DOI] [PubMed] [Google Scholar]
  63. Jurgens C.K., Barton D.J., Sharma N., Morasco B.J., Ogram S.A., Flanegan J.B. 2Apro is a multifunctional protein that regulates the stability, translation and replication of poliovirus RNA. Virology. 2006;345:346–357. doi: 10.1016/j.virol.2005.09.067. [DOI] [PubMed] [Google Scholar]
  64. Katz S.L. Polio — new challenges in 2006. J Clin Virol. 2006;36:163–165. doi: 10.1016/j.jcv.2006.03.003. [DOI] [PubMed] [Google Scholar]
  65. Kirchweger R., Ziegler E., Lamphear B.J., Waters D., Liebig H.D., Sommergruber W., Sobrino F., Hohenadl C., Blaas D., Rhoads R.E., Skern T. Foot-and-mouth disease virus leader proteinase: purification of the Lb form and determination of its cleavage site on eIF-4 gamma. J Virol. 1994;68:5677–5684. doi: 10.1128/jvi.68.9.5677-5684.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
  66. Kleina L.G., Grubman M.J. Antiviral effects of a thiol protease inhibitor on foot-and-mouth disease virus. J Virol. 1992;66:7168–7175. doi: 10.1128/jvi.66.12.7168-7175.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
  67. Koenig H., Rosenwirth B. Purification and partial characterization of poliovirus protease 2A by means of a functional assay. J Virol. 1988;62:1243–1250. doi: 10.1128/jvi.62.4.1243-1250.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  68. Kuehnel E., Cencic R., Foeger N., Skern T. Foot-and-mouth disease virus leader pro-teinase: specificity at the P2 and P3 positions and comparison with other papain-like enzymes. Biochemistry. 2004;43:11482–11490. doi: 10.1021/bi049340d. [DOI] [PubMed] [Google Scholar]
  69. Lall M.S., Jain R.P., Vederas J.C. Inhibitors of 3C cysteine proteinases from picorna-viridae. Curr Top Med Chem. 2004;4:1239–1253. doi: 10.2174/1568026043387836. [DOI] [PubMed] [Google Scholar]
  70. Lau S.K., Yip C.C., Tsoi H.W., Lee R.A., So L.Y., Lau Y.L., Chan K.H., Woo P.C., Yuen K.Y. Clinical features and complete genome characterization of a distinct human rhinovirus (HRV) genetic cluster, probably representing a previously undetected HRV species, HRV-C, associated with acute respiratory illness in children. J Clin Microbiol. 2007;45:3655–3664. doi: 10.1128/JCM.01254-07. [DOI] [PMC free article] [PubMed] [Google Scholar]
  71. Lee E.S., Lee W.G., Yun S.H., Rho S.H., Im I., Yang S.T., Sellamuthu S., Lee Y.J., Kwon S.J., Park O.K., Jeon E.S., Park W.J., Kim Y.C. Development of potent inhibitors of the coxsackievirus 3C protease. Biochem Biophys Res Commun. 2007;358:7–11. doi: 10.1016/j.bbrc.2007.03.208. [DOI] [PubMed] [Google Scholar]
  72. Li W., Ross-Smith N., Proud C.G., Belsham G.J. Cleavage of translation initiation factor 4AI (eIF4AI) but not eIF4AII by foot-and-mouth disease virus 3C protease: identification of the eIF4AI cleavage site. FEBS Lett. 2001;507:1–5. doi: 10.1016/s0014-5793(01)02885-x. [DOI] [PubMed] [Google Scholar]
  73. Li X., Lu H.H., Mueller S., Wimmer E. The C-terminal residues of poliovirus proteinase 2A(pro) are critical for viral RNA replication but not for cis- or trans-proteolytic cleavage. J Gen Virol. 2001;82:397–408. doi: 10.1099/0022-1317-82-2-397. [DOI] [PubMed] [Google Scholar]
  74. Liebig H.-D., Ziegler E., Yan R., Hartmuth K., Klump H., Kowalski H., Blaas D., Sommergruber W., Frasel L., Lamphear B., Rhoads R., Kuechler E., Skern T. Purification of two picornaviral 2A proteinases: interaction with eIF-4gamma and influence on in vitro translation. Biochemistry. 1993;32:7581–7588. doi: 10.1021/bi00080a033. [DOI] [PubMed] [Google Scholar]
  75. Lloyd R.E. Translational control by viral proteinases. Virus Res. 2006;119:76–88. doi: 10.1016/j.virusres.2005.10.016. [DOI] [PMC free article] [PubMed] [Google Scholar]
  76. Lyle J.M., Clewell A., Richmond K., Richards O.C., Hope D.A., Schultz S.C., Kirkegaard K. Similar structural basis for membrane localization and protein priming by an RNA-dependent RNA polymerase. J Biol Chem. 2002;277:16324–16331. doi: 10.1074/jbc.M112429200. [DOI] [PubMed] [Google Scholar]
  77. MacLennan C., Dunn G., Huissoon A.P., Kumararatne D.S., Martin J., O'Leary P., Thompson R.A., Osman H., Wood P., Minor P., Wood D.J., Pillay D. Failure to clear persistent vaccine-derived neurovirulent poliovirus infection in an immunodeficient man. Lancet. 2004;363:1509–1513. doi: 10.1016/S0140-6736(04)16150-3. [DOI] [PubMed] [Google Scholar]
  78. Marcotte L.L., Wass A.B., Gohara D.W., Pathak H.B., Arnold J.J., Filman D.J., Cameron C.E., Hogle J.M. Crystal structure of poliovirus 3CD protein: virally encoded protease and precursor to the RNA-dependent RNA polymerase. J Virol. 2007;81:3583–3596. doi: 10.1128/JVI.02306-06. [DOI] [PMC free article] [PubMed] [Google Scholar]
  79. Matthews D.A., Smith W.W., Ferre R.A., Condon B., Budahazi G., Sisson W., Villafranca J.E., Janson C.A., McElroy H.E., Gribskov C.L., Worland S. Structure of human rhi-novirus 3C protease reveals a trypsin-like polypeptide fold, RNA-binding site, and means for cleaving precursor polyprotein. Cell. 1994;77:761–771. doi: 10.1016/0092-8674(94)90059-0. [DOI] [PubMed] [Google Scholar]
  80. Matthews D.A., Dragovich P.S., Webber S.E., Fuhrman S.A., Patick A.K., Zalman L.S., Hendrickson T.F., Love R.A., Prins T.J., Marakovits J.T., Zhou R., Tikhe J., Ford C.E., Meador J.W., Ferre R.A., Brown E.L., Binford S.L., Brothers M.A., De Lisle D.M., Worland S.T. Structure-assisted design of mechanism-based irreversible inhibitors of human rhinovirus 3C protease with potent antiviral activity against multiple rhinovirus sero-types. Proc Natl Acad Sci USA. 1999;96:11000–11007. doi: 10.1073/pnas.96.20.11000. [DOI] [PMC free article] [PubMed] [Google Scholar]
  81. Mayer C., Neubauer D., Nchinda A.T., Cencic R., Trompf K., Skern T. Residue L143 of the foot-and-mouth disease virus leader proteinase is a determinant of cleavage specificity. J Virol. 2008;82:4656–4659. doi: 10.1128/JVI.02077-07. [DOI] [PMC free article] [PubMed] [Google Scholar]
  82. McErlean P., Shackelton L.A., Lambert S.B., Nissen M.D., Sloots T.P., Mackay I.M. Characterisation of a newly identified human rhinovirus, HRV-QPM, discovered in infants with bronchiolitis. J Clin Virol. 2007;39:67–75. doi: 10.1016/j.jcv.2007.03.012. [DOI] [PMC free article] [PubMed] [Google Scholar]
  83. Moerke N.J., Aktas H., Chen H., Cantel S., Reibarkh M.Y., Fahmy A., Gross J.D., Degterev A., Yuan J., Chorev M., Halperin J.A., Wagner G. Small-molecule inhibition of the interaction between the translation initiation factors eIF4E and eIF4G. Cell. 2007;128:257–267. doi: 10.1016/j.cell.2006.11.046. [DOI] [PubMed] [Google Scholar]
  84. Morace G., Kusov Y., Dzagurov G., Beneduce F., Gauss-Muller V. The unique role of domain 2A of the hepatitis A virus precursor polypeptide P1-2A in viral morphogenesis. BMB Rep. 2008;41:678–683. doi: 10.5483/bmbrep.2008.41.9.678. [DOI] [PubMed] [Google Scholar]
  85. Morley S.J., Curtis P.S., Pain V.M. eIF4G: translation's mystery factor begins to yield its secrets. RNA. 1997;3:1085–1104. [PMC free article] [PubMed] [Google Scholar]
  86. Mosimann S.C., Cherney M.M., Sia S., Plotch S., James M.N.G. Refined X-ray crystallographic structure of the poliovirus 3C gene product. J Mol Biol. 1997;273:1032–1047. doi: 10.1006/jmbi.1997.1306. [DOI] [PubMed] [Google Scholar]
  87. Neznanov N., Chumakov K.M., Neznanova L., Almasan A., Banerjee A.K., Gudkov A.V. Proteolytic cleavage of the p65-RelA subunit of NF-kappaB during poliovirus infection. J Biol Chem. 2005;280:24153–24158. doi: 10.1074/jbc.M502303200. [DOI] [PubMed] [Google Scholar]
  88. N.R.C. Committee on Development of a Polio Antiviral and Its Potential Role in Global Poliomyelitis Eradication . Exploring the Role of Antiviral Drugs in the Eradication of Polio: Workshop Report. Washington, DC.: The National Academies Press; 2006. [Google Scholar]
  89. Ohlenschlager O., Wohnert J., Bucci E., Seitz S., Hafner S., Ramachandran R., Zell R., Gorlach M. The structure of the stemloop D subdomain of coxsackievirus B3 cloverleaf RNA and its interaction with the proteinase 3C. Structure. 2004;12:237–248. doi: 10.1016/j.str.2004.01.014. [DOI] [PubMed] [Google Scholar]
  90. Park N., Katikaneni P., Skern T., Gustin K.E. Differential targeting of nuclear pore complex proteins in poliovirus-infected cells. J Virol. 2008;82:1647–165. doi: 10.1128/JVI.01670-07. [DOI] [PMC free article] [PubMed] [Google Scholar]
  91. Patick A.K. Rhinovirus chemotherapy. Antiviral Res. 2006;71:391–396. doi: 10.1016/j.antiviral.2006.03.011. [DOI] [PMC free article] [PubMed] [Google Scholar]
  92. Patick A.K., Brothers M.A., Maldonado F., Binford S., Maldonado O., Fuhrman S., Petersen A., Smith G.A., 3rd, Zalman L.S., Burns-Naas L.A., Tran J.Q. In vitro antiviral activity and single-dose pharmacokinetics in humans of a novel, orally bioavailable inhibitor of human rhinovirus 3C protease. Antimicrob Agents Chemother. 2005;49:2267–2275. doi: 10.1128/AAC.49.6.2267-2275.2005. [DOI] [PMC free article] [PubMed] [Google Scholar]
  93. Pelham H.R.B. Translation of encephalomyocarditis virus RNA in vitro yields an active proteolytic processing enzyme. Eur J Biochem. 1978;85:457–462. doi: 10.1111/j.1432-1033.1978.tb12260.x. [DOI] [PubMed] [Google Scholar]
  94. Perera R., Daijogo S., Walter B.L., Nguyen J.H., Semler B.L. Cellular protein modification by poliovirus: the two faces of poly(rC)-binding protein. J Virol. 2007;81:8919–8932. doi: 10.1128/JVI.01013-07. [DOI] [PMC free article] [PubMed] [Google Scholar]
  95. Peters H., Kusov Y.Y., Meyer S., Benie A.J., Bauml E., Wolff M., Rademacher C., Peters T., Gauss-Muller V. Hepatitis A virus proteinase 3C binding to viral RNA: correlation with substrate binding and enzyme dimerization. Biochem J. 2005;385:363–370. doi: 10.1042/BJ20041153. [DOI] [PMC free article] [PubMed] [Google Scholar]
  96. Petersen J.F., Cherney M.M., Liebig H.-D., Skern T., Kuechler E., James M.N. The structure of the 2A proteinase from a common cold virus: a proteinase responsible for the shut-off of host-cell protein synthesis. EMBO J. 1999;18:5463–5475. doi: 10.1093/emboj/18.20.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
  97. Racaniello V.R. Picornaviridae: The viruses and their replication. In: Fields B.N., Knipe D.M., Howley P.M., editors. Fields Virology. Philadelphia, PA: Lippincott Williams & Wilkins; 2007. pp. 795–838. [Google Scholar]
  98. Renwick N., Schweiger B., Kapoor V., Liu Z., Villari J., Bullmann R., Miething R., Briese T., Lipkin W.I. A recently identified rhinovirus genotype is associated with severe respiratory-tract infection in children in Germany. J Infect Dis. 2007;196:1754–1760. doi: 10.1086/524312. [DOI] [PMC free article] [PubMed] [Google Scholar]
  99. Robertson S.E., Chan C., Kim-Farley R., Ward N. Worldwide status of poliomyelitis in 1986, 1987 and 1988, and plans for its global eradication by the year 2000. World Health Stat. 1990;Q43:80–90. [PubMed] [Google Scholar]
  100. Sarkany Z., Polgar L. The unusual catalytic triad of poliovirus protease 3C. Biochemistry. 2003;42:516–522. doi: 10.1021/bi027004w. [DOI] [PubMed] [Google Scholar]
  101. Savolainen C., Blomqvist S., Mulders M.N., Hovi T. Genetic clustering of all 102 human rhinovirus prototype strains: serotype 87 is close to human enterovirus 70. J Gen Virol. 2002;83:333–340. doi: 10.1099/0022-1317-83-2-333. [DOI] [PubMed] [Google Scholar]
  102. Seipelt J., Liebig H.D., Sommergruber W., Gerner C., Kuechler E. 2A proteinase of human rhinovirus cleaves cytokeratin 8 in infected HeLa cells. J Biol Chem. 2000;275:20084–20089. doi: 10.1074/jbc.275.26.20084. [DOI] [PubMed] [Google Scholar]
  103. Semler B.L. Resistance is futile. Nat Genet. 2005;37:665–666. doi: 10.1038/ng0705-665. [DOI] [PMC free article] [PubMed] [Google Scholar]
  104. Semler B.L., Wimmer E. Molecular Biology of Picornaviruses. Washington, DC: ASM Press; 2002. [Google Scholar]
  105. Skern T., Sommergruber W., Blaas D., Gruendler P., Frauendorfer F., Pieler C., Fogy I., Kuechler E. Human rhinovirus 2: complete nucleotide sequence and proteolytic processing signals in the capsid protein region. Nucl Acids Res. 1985;13:2111–2126. doi: 10.1093/nar/13.6.2111. [DOI] [PMC free article] [PubMed] [Google Scholar]
  106. Skern T., Sommergruber W., Auer H., Volkmann P., Zorn M., Liebig H.-D., Fessl F., Blaas D., Kuechler E. Substrate requirements of a human rhinoviral 2A proteinase. Virology. 1991;181:46–54. doi: 10.1016/0042-6822(91)90468-q. [DOI] [PubMed] [Google Scholar]
  107. Skern T., Fita I., Guarne A. A structural model of picornavirus leader proteinases based on papain and bleomycin hydrolase. J Gen Virol. 1998;79:301–307. doi: 10.1099/0022-1317-79-2-301. [DOI] [PubMed] [Google Scholar]
  108. Skern T., Hampoelz B., A. Guarné, Fita I., Bergmann E., Petersen J., James M.N.G. Structure and function of picornavirus proteinases. In: Semler B.L., Wimmer E., editors. Molecular Biology of Picornaviruses. Washington, DC: ASM Press; 2002. pp. 199–212. [Google Scholar]
  109. Sommergruber W., Zorn M., Blaas D., Fessl F., Volkmann P., Maurer-Fogy I., Pallai P., Merluzzi V., Matteo M., Skern T., et al. Polypeptide 2A of human rhinovirus type 2: identification as a protease and characterization by mutational analysis. Virology. 1989;169:68–77. doi: 10.1016/0042-6822(89)90042-1. [DOI] [PubMed] [Google Scholar]
  110. Sousa C., Schmid E.M., Skern T. Defining residues involved in human rhinovirus 2A proteinase substrate recognition. FEBS Lett. 2006;580:5713–5717. doi: 10.1016/j.febslet.2006.09.023. [DOI] [PubMed] [Google Scholar]
  111. Strebel K., Beck E. A second protease of foot-and mouth disease virus. J Virol. 1986;58:893–899. doi: 10.1128/jvi.58.3.893-899.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  112. Svitkin Y.V., Gradi A., Imataka H., Morino S., Sonenberg N. Eukaryotic initiation factor 4GII (eIF4GII), but not eIF4GI, cleavage correlates with inhibition of host cell protein synthesis after human rhinovirus infection. J Virol. 1999;73:3467–3472. doi: 10.1128/jvi.73.4.3467-3472.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  113. Sweeney T.R., Roque-Rosell N., Birtley J.R., Leatherbarrow R.J., Curry S. Structural and mutagenic analysis of foot-and-mouth disease virus 3C protease reveals the role of the beta-ribbon in proteolysis. J Virol. 2007;81:115–124. doi: 10.1128/JVI.01587-06. [DOI] [PMC free article] [PubMed] [Google Scholar]
  114. Tesar M., Marquardt O. Foot-and-mouth disease virus protease 3C inhibits cellular transcription and mediates cleavage of histone H3. Virology. 1990;174:364–374. doi: 10.1016/0042-6822(90)90090-e. [DOI] [PubMed] [Google Scholar]
  115. Thomson G.R., Vosloo W., Bastos A.D. Foot and mouth disease in wildlife. Virus Res. 2003;91:145–161. doi: 10.1016/s0168-1702(02)00263-0. [DOI] [PubMed] [Google Scholar]
  116. Toyoda H., Nicklin M.J., Murray M.G., Anderson C.W., Dunn J.J., Studier F.W., Wimmer E. A second virus-encoded proteinase involved in proteolytic processing of poliovirus polyprotein. Cell. 1986;45:761–770. doi: 10.1016/0092-8674(86)90790-7. [DOI] [PubMed] [Google Scholar]
  117. Turner R.B. Rhinovirus: more than just a common cold virus. J Infect Dis. 2007;195:765–766. doi: 10.1086/511829. [DOI] [PubMed] [Google Scholar]
  118. Ventoso I., MacMillan S.E., Hershey J.W., Carrasco L. Poliovirus 2A proteinase cleaves directly the eIF-4G subunit of eIF-4F complex. FEBS Lett. 1998;435:79–83. doi: 10.1016/s0014-5793(98)01027-8. [DOI] [PubMed] [Google Scholar]
  119. Wells J.C., McClendon C.L. Reaching for high-hanging fruit in drug discovery at protein-protein interfaces. Nature. 2007;450:1001–1009. doi: 10.1038/nature06526. [DOI] [PubMed] [Google Scholar]
  120. Witherell G. AG-7088 Pfizer. Curr Opin Investig Drugs. 2000;1:297–302. [PubMed] [Google Scholar]
  121. Yalamanchili P., Banerjee R., Dasgupta A. Poliovirus-encoded protease 2APro cleaves the TATA-binding protein but does not inhibit host cell RNA polymerase II transcription in vitro. J Virol. 1997;71:6881–6886. doi: 10.1128/jvi.71.9.6881-6886.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
  122. Yin J., Bergmann E.M., Cherney M.M., Lall M.S., Jain R.P., Vederas J.C., James M.N. Dual modes of modification of hepatitis A virus 3C protease by a serine-derived beta-lactone: selective crystallization and formation of a functional catalytic triad in the active site. J Mol Biol. 2005;354:854–871. doi: 10.1016/j.jmb.2005.09.074. [DOI] [PMC free article] [PubMed] [Google Scholar]
  123. Yoneyama T., Yoshida H., Shimizu H., Yoshii K., Nagata N., Kew O., Miyamura T. Neurovirulence of sabin 1-derived polioviruses isolated from an immunodeficient patient with prolonged viral excretion. Dev Biol (Basel) 2001;105:93–98. [PubMed] [Google Scholar]
  124. Ypma-Wong M.F., Dewalt P.G., Johnson V.H., Lamb J.G., Semler B.L. Protein 3CD is the major poliovirus proteinase responsible for cleavage of the P1 capsid precursor. Virology. 1988;166:265–270. doi: 10.1016/0042-6822(88)90172-9. [DOI] [PubMed] [Google Scholar]
  125. Zell R., Sidigi K., Bucci E., Stelzner A., Gorlach M. Determinants of the recognition of enteroviral cloverleaf RNA by coxsackievirus B3 proteinase 3C. RNA. 2002;8:188–201. doi: 10.1017/s1355838202012785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  126. Zhang B., Morace G., Gauss-Muller V., Kusov Y. Poly(A) binding protein, C-terminally truncated by the hepatitis A virus proteinase 3C, inhibits viral translation. Nucleic Acids Res. 2007;35:5975–5984. doi: 10.1093/nar/gkm645. [DOI] [PMC free article] [PubMed] [Google Scholar]
  127. Zhang B., Seitz S., Kusov Y., Zell R., Gauss-Muller V. RNA interaction and cleavage of poly(C)-binding protein 2 by hepatitis A virus protease. Biochem Biophys Res Commun. 2007;364:725–730. doi: 10.1016/j.bbrc.2007.09.133. [DOI] [PubMed] [Google Scholar]
  128. Ziegler E., Borman A.M., Deliat F.G., Liebig H.-D., Jugovic D., Kean K.M., Skern T., Kuechler E. Picornavirus 2A proteinase-mediated stimulation of internal initiation of translation is dependent on enzymatic activity and the cleavage products of cellular proteins. Virology. 1995;213:549–557. doi: 10.1016/s0042-6822(95)90001-2. [DOI] [PubMed] [Google Scholar]

Articles from Viral Proteases and Antiviral Protease Inhibitor Therapy are provided here courtesy of Nature Publishing Group

RESOURCES